Evolutionarily Dynamic Alternative Splicing of GPR56 Regulates Regional Cerebral Cortical Patterning
Open accessAbstract
Development of surface folds of the human brain is controlled in sections. [Also see Perspective by Rash and Rakic ]
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- Findingown data
Dominant-negative RFX abrogates normal but not mutant e1m promoter activity in E13.5 mouse cortical cultures.
“Dominant-negative RFX abrogates normal, but not mutant, e1m promoter activity on embryonic day 13.5 (E13.5) in mouse cortical cultures”
Quote in the paperSubstantial claim - Findingown data
The two Irish-American families share the mutation on one chromosomal haplotype, indicating a common founder.
“The two Irish-American families carry the mutation on the same chromosomal haplotype, which reflects a common founder.”
Quote in the paperNot a substantial claim - Findingown data
The mutated element is located less than 150 base pairs upstream of the transcriptional start site of noncoding exon 1m of GPR56.
“The element is located <150 bp upstream of the transcriptional start site of noncoding exon 1m (e1m) of GPR56”
Quote in the paperSubstantial claim - Findingown data
The same 23-kb construct containing the 15-bp deletion drives expression in medial but not lateral cortex or lateral ganglionic eminence.
“In contrast, the 23-kb construct containing the 15-bp deletion drives expression in medial, but not lateral, cortex or lateral ganglionic eminence”
Quote in the paperSubstantial claim - Findingown data
Yeast one-hybrid screening with the human cis-regulatory element as bait identified multiple yeast colonies encoding members of the RFX transcription factor family.
“we performed yeast one-hybrid (Y1H) screening of a mouse forebrain cDNA library with the human cis-regulatory element as bait and obtained multiple yeast colonies encoding members of the regulatory factor X (Rfx) transcription factor family”
Quote in the paperSubstantial claim
- Findingown data
RFX1 and GPR56 colocalize in germinal zones of fetal human brain.
“RFX1 and GPR56 colocalize in germinal zones of fetal human brain”
Quote in the paperSubstantial claim - Findingown data
ChIP-seq confirmed RFX3 binding to the element.
“Chromatin immunoprecipitation sequencing confirmed RFX3 binding to the element”
Quote in the paperSubstantial claim - Findingown data
A 23-kb human GPR56 upstream region driving GFP in transgenic mice recapitulates the location and relative amount of endogenous mouse GPR56 protein expression in the entire central nervous system, including neocortex.
“This construct drives GFP expression in the entire central nervous system, including neocortex, and recapitulates the location and relative amount of expression of endogenous mouse GPR56 protein”
Quote in the paperSubstantial claim - Findingown data
A 15-base-pair deletion in a conserved non-exonic element of GPR56 was identified in all five individuals with perisylvian polymicrogyria from three families.
“we sequenced 38 conserved non-exonic elements (table S2), in one of which we identified a small deletion in all five individuals. The mutated element normally contains two copies of a 15–base pair (bp) tandem repeat, but all affected individuals have a homozygous deletion of one 15-bp repeat”
Quote in the paperSubstantial claim - Findingown data
The mouse e1m promoter drives β-gal expression broadly in the nervous system in diverse cell types.
“The mouse e1m promoter drives β-gal expression broadly in the nervous system in diverse cell types”
Quote in the paperSubstantial claim - Findingown data
In utero electroporation of a plasmid encoding GPR56 caused cells to persist in proliferative zones compared with cells expressing GFP alone.
“In utero electroporation (at E13.5 with analysis 48 hours later at E15.5) of a plasmid encoding GPR56 (as well as GFP, to mark the cells) caused cells to persist in proliferative zones compared with cells expressing GFP alone”
Quote in the paperSubstantial claim - Findingown data
Mice carrying a transgene that directs overexpression of human GPR56 show increased mitotic progenitor cells and intermediate progenitor cells.
“mice carrying a transgene that directs overexpression of human GPR56 show increased mitotic progenitor cells and intermediate progenitor cells”
Quote in the paperSubstantial claim - Findingnone given
The cis-regulatory element sequence is found only at the e1m locus in GPR56 and not elsewhere in the genome.
“The cis-regulatory element sequence is only found at the e1m locus in GPR56 but not elsewhere in the genome.”
Quote in the paperNot a substantial claim - Findingown data
In contrast to more than 17 alternative first exons in humans, only five noncoding first exons were found in the mouse Gpr56 gene.
“In contrast to the >17 alternative first exons in humans, we found only five noncoding first exons in the mouse Gpr56 gene”
Quote in the paperSubstantial claim - Findingown data
Even where the pia is intact, neocortical thickness and organization are irregular, with occasional thin regions in Gpr56 knockout mice.
“even where the pia is intact, we found that neocortical thickness and organization are irregular, with occasional thin regions in Gpr56 knockout mice”
Quote in the paperSubstantial claim - Findingown data
E1m promoters from marmoset, dolphin, and cat drive expression patterns generally similar to human.
“E1m promoters from marmoset, dolphin, and cat drive expression patterns generally similar to human.”
Quote in the paperSubstantial claim - Premisecitation
Genetic ablation of Rfx4 decreases Gpr56 expression in developing mouse brain.
“genetic ablation of Rfx4 decreases Gpr56 expression in developing mouse brain (14).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] Zhang D J Neurochem 98 860 875 2006 16893423 source
Not checked in the free run.
- Interpretationreasoning
Multiple RFX proteins regulate the e1m element.
“which suggests that multiple RFX proteins regulate the element.”
Quote in the paperSubstantial claim - Interpretationown data
The shared expression patterns in the four mammals that have a Sylvian fissure suggest that elaboration of GPR56 noncoding regulation is consistent with the larger number of noncoding first exons in gyrencephalic mammals and humans.
“The shared expression patterns in the four mammals that have a Sylvian fissure (Fig. 4C) suggest that elaboration of GPR56 noncoding regulation is consistent with the larger number of noncoding first exons in gyrencephalic mammals and humans.”
Quote in the paperSubstantial claim - Interpretationreasoning
Elaboration of additional alternative splice forms provides a mechanism for potentially independent evolution of these multiple forms.
“Elaboration of additional alternative splice forms provides a mechanism for potentially independent evolution of these multiple forms.”
Quote in the paperSubstantial claim - Premisecitation
GPR56 protein is most highly expressed in progenitors in the ventricular and subventricular zones during neurogenesis in mice.
“GPR56 protein is most highly expressed in progenitors in the ventricular and subventricular zones during neurogenesis in mice (16, 18).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationown data
GPR56 expression levels regulate progenitor proliferation in the neocortex.
“Impairment and overexpression of GPR56 show that its expression regulates proliferation.”
- Also stated in: § Abstract · plain
“Our studies show that levels of GPR56 control proliferation of progenitors in the neocortex.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Interpretationreasoning
In humans, additional elements besides the 300-bp e1m promoter region are required to drive the full complement of GPR56 expression.
“which suggests that, in humans, additional elements besides the 300-bp e1m promoter region are required to drive the full complement of GPR56 expression.”
Quote in the paperSubstantial claim - Interpretationown data
The simple 300-bp mouse e1m promoter is sufficient to recapitulate major features of endogenous mouse GPR56 expression.
“which suggests that this simple 300-bp e1m promoter is sufficient to recapitulate major features of the endogenous mouse GPR56 expression”
Quote in the paperSubstantial claim - Interpretationreasoning
Selective GPR56 loss causes strikingly regional defects of cortical development.
“Selective GPR56 loss causes strikingly regional defects of cortical development.”
Quote in the paperSubstantial claim - Interpretationreasoning
GPR56 likely influences progenitor proliferation by stabilizing the basal process of radial neuroepithelial progenitors.
“GPR56 likely influences progenitor proliferation by stabilizing the basal process of radial neuroepithelial progenitors”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [16] Li S J Neurosci 28 5817 5826 2008 18509043 PMC2504715 source
Not checked in the free run.
- cites [17] Luo R Proc Natl Acad Sci USA 108 12925 12930 2011 21768377 PMC3150909 source
Not checked in the free run.
- cites [22] Radakovits R Barros CS Belvindrah R Patton B Müller U J Neurosci 29 7694 7705 2009 19535581 PMC2738639 source
Not checked in the free run.
- Interpretationreasoning
The cis-regulatory element emerged after placental and nonplacental mammals diverged 85 to 100 million years ago.
“which suggests that it emerged after placental and nonplacental mammals diverged 85 to 100 million years ago”
Quote in the paperSubstantial claim- Rests on an assumption: Placental and nonplacental mammals diverged 85 to 100 million years ago.
- Interpretationown data
The data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and potentially neocortex evolution.
“Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution.”
Quote in the paperSubstantial claim - Premisecitation
E1m shows homology at its 3' end to LINE-4/RTE, a family of retrotransposons active in early mammals after divergence from marsupials.
“E1m itself shows homology at its 3′ end to a long interspersed nuclear element (LINE)–4/RTE, a family of retrotransposons active in early mammals after divergence from marsupials (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Mikkelsen TS Nature 447 167 177 2007 17495919 source
Not checked in the free run.
- May combine two claims. 16
May combine two claims.
Findingown dataThe noncoding first exons of GPR56 have distinct expression profiles; e1m is the most robustly transcribed first exon in fetal human brain, and several other alternative transcripts are also expressed in fetal and adult brain.
“The diverse noncoding first exons have distinct expression profiles, with e1m being the most robustly transcribed first exon in fetal human brain but with several other alternative transcripts also expressed in fetal and adult brain”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe deletion is heterozygous in unaffected parents and absent from thousands of control chromosomes.
“The deletion is heterozygous in parents of the affected individuals, who manifest no obvious clinical signs, and is absent from thousands of control chromosomes in the Single-Nucleotide Polymorphism Database and 1000 Genomes database.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataRFX1 and RFX3 bind the normal element in vitro, and the 15-bp deletion decreases binding by 60 to 70%.
“RFX1 and RFX3 bind the normal element in vitro, with binding decreased 60 to 70% by the 15-bp deletion”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe Turkish family carries the same deletion on a distinct haplotype, indicating that the mutation arose independently.
“It is noteworthy that the Turkish family carries the same deletion on a distinct haplotype, which indicates that the mutation arose independently”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationRFX and GPR56 expression patterns are correlated, with RFX3 and RFX7 most prominent in human ventrolateral prefrontal cortex, the region affected in perisylvian polymicrogyria.
“RFX and GPR56 expression patterns are correlated (fig. S5, A and B) (15), with RFX3 and RFX7 most prominent in human ventrolateral prefrontal cortex, the region affected in perisylvian polymicrogyria”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Kang HJ Nature 478 483 489 2011 22031440 PMC3566780 source
Not checked in the free run.
May combine two claims.
Findingown dataAnother noncoding GPR56 exon, exon 2, is present only in primates and derives from a primate-specific Alu insertion.
“Another noncoding GPR56 exon (exon 2), present only in primates, derives from a primate-specific Alu insertion”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataGpr56 knockout mice show fewer PH3-positive mitotic progenitor cells and TBR2-positive intermediate progenitors than wild-type mice in the neocortex at E14.5.
“Gpr56 knockout mice show fewer phosphohistone H3 (PH3)–positive mitotic progenitor cells and TBR2-positive intermediate progenitors than wild-type mice in the neocortex at E14.5.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe cis-regulatory element upstream of GPR56 e1m is present in genomes of all placental mammals but absent from monotremes, marsupials, and non-mammals.
“The cis-regulatory element upstream of GPR56 e1m is found in genomes of all placental mammals, but not monotremes, marsupials, or non-mammals”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe human e1m promoter has a variety of deletions and single-nucleotide variants relative to the mouse sequence and drives much more limited expression in rostral-lateral cortex.
“the corresponding human e1m promoter has a variety of deletions and single-nucleotide variants, relative to the mouse sequence (fig. S6A), and drives much more limited expression in rostral-lateral cortex”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationGPR56 expression in developing human and marmoset neocortex is highest in the ventricular zone and in the outer subventricular zone, which is expanded in mammals with larger brains.
“GPR56 expression in developing human and marmoset neocortex is highest in the ventricular zone, as well as in the outer subventricular zone, which is expanded in mammals with larger brains”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe cis-regulatory element upstream of e1m drives GPR56 expression in perisylvian and lateral cortex, and its disruption with impaired e1m expression causes perisylvian malformation.
“These data suggest that the cis-regulatory element upstream of e1m drives GPR56 expression in the perisylvian and lateral cortex, whereas disruption of the element, with consequent impairment of e1m expression, causes the perisylvian malformation.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationGPR56 encodes an adhesion heterotrimeric G protein-coupled receptor that is highly expressed in cortical progenitors and binds extracellular matrix proteins.
“GPR56 encodes an adhesion heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor that is highly expressed in cortical progenitors (7, 16) and binds extracellular matrix proteins (17).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [7] Piao X Science 303 2033 2036 2004 15044805 source
Not checked in the free run.
- cites [16] Li S J Neurosci 28 5817 5826 2008 18509043 PMC2504715 source
Not checked in the free run.
- cites [17] Luo R Proc Natl Acad Sci USA 108 12925 12930 2011 21768377 PMC3150909 source
Not checked in the free run.
May combine two claims.
PremisecitationLoss of GPR56 disrupts radial glia and causes breaches in the pial basement membrane, through which some neurons over-migrate.
“Loss of GPR56 disrupts radial glia and causes breaches in the pial basement membrane, through which some neurons over-migrate (9, 16).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationPostmortem analysis of a human with biallelic GPR56 coding mutations showed a very thin cortex, suggesting potential roles of GPR56 in neurogenesis.
“Postmortem analysis of a human with biallelic GPR56 coding mutations showed a very thin cortex, which suggested potential roles of GPR56 in neurogenesis as well (9).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] Bahi-Buisson N Brain 133 3194 3209 2010 20929962 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe elaboration of the GPR56 locus in gyrencephalic mammals, especially humans, to produce many alternative splice forms with diverse expression patterns presents GPR56 as a key target that could influence the dramatic changes in shape and folding that characterize the forebrain of many mammals.
“The elaboration of the GPR56 locus in gyrencephalic mammals, and especially humans, to produce many alternative splice forms with diverse expression patterns presents GPR56 as a key target that could influence the dramatic changes in shape and folding that characterize the forebrain of many mammals.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningGPR56 acquired many noncoding upstream exons and generated alternative splice forms with distinct expression patterns in the lineage leading to humans, and transposable element insertion contributed to this diversity.
“Thus, GPR56 acquired many noncoding upstream exons and generated alternative splice forms with distinct expression patterns (fig. S2, B and D), in the lineage leading to humans. Transposable element insertion played a role in generating this diversity.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The mechanisms of cortical gyrification and the formation of specialized cortical regions are poorly understood.
“the genetic and evolutionary mechanisms of cortical gyrification are poorly understood”
“it is unsolved how these cortical regions form and how human cortical regions evolved from those of prehuman ancestors.”
The paper relies on this without support.
Abnormal gyrification invariably indicates abnormal cortical development.
“Abnormal gyrification, such as polymicrogyria (too many small gyri), invariably signals abnormal cortical development”
The paper relies on this without support.
Placental and nonplacental mammals diverged 85 to 100 million years ago.
“diverged 85 to 100 million years ago”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Extensive variation in cis-regulation of GPR56 is observed due to expansion of number of transcriptional start sites in human GPR56 (17) compared to mouse Gpr56 (5).
“For example, extensive variation in the cis-regulation of GPR56, a gene that promotes neural progenitor proliferation (Bae et al., 2014), is observed due to the expansion of the number of transcriptional start sites present in human GPR56 (17 start sites) as compared to its mouse ortholog Gpr56 (5 start sites; Figure 7A).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Bae et al., 2014
Human-specific expansion, deletion, and de novo emergence of regulatory elements are observed.
“In addition to evolutionary changes in transcription factor binding sites, human-specific expansion, deletion, and de novo emergence of regulatory elements are also observed (Bae et al., 2014).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Bae et al., 2014
The cis-element of human alternative transcriptional start site E1m can drive expression of a reporter gene in radial glia cells throughout embryonic neocortex of transgenic mouse.
“The cis-element of one of these human alternative transcriptional start sites (E1m) can drive expression of a reporter gene in RG cells throughout the embryonic neocortex of a transgenic mouse (Figure 7B).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Bae et al., 2014
A 15 base pair deletion of E1m cis-element caused perysylvian microgyria in humans and affected rostro-lateral GPR56 expression in mouse.
“Moreover, a 15 base pair deletion of the E1m cis-element caused perysylvian microgyria in humans and affected rostro-lateral GPR56 expression in mouse (Figures 7C and D).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Bae et al., 2014
Further experiments with sequences from other mammals with prominent sylvian fissure and gyrencephalic brain recapitulated this expression pattern, suggesting GPR56 was important for evolutionary expansion of perisylvian neocortex.
“Further experiments with sequences found in other mammals with a prominent sylvian fissure and gyrencephalic brain recapitulated this pattern of expression, suggesting that GPR56 was important for the evolutionary expansion of the perisylvian neocortex, a region involved in the processing of language and speech and other higher-order cognitive functions.”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Bae et al., 2014
The human noncoding element directs gene expression in a highly restricted pattern, whereas the mouse element directs more diffuse expression.
“Intriguingly, the human noncoding element directs gene expression in a highly restricted pattern, whereas the mouse element directs more diffuse expression.”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Bae et al., 2014
Human GPR56 has at least 17 alternative promoters, whereas mouse Gpr56 has only a handful.
“It turned out that the human GPR56 has at least 17 alternative promoters, whereas mouse Gpr56 has only a handful.”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Bae et al., 2014
Many complex alternative promoters and exons of human GPR56 were derived from LINEs and SINEs.
“For example, many of the complex alternative promoters and exons of human GPR56 were derived from LINEs and SINEs (Bae et al., 2014).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Bae et al., 2014
Polymicrogyria restricted to neocortical areas surrounding the Sylvian fissure including Broca's area was identified, and the causative mutation in the GPR56 locus disrupts a noncoding element that is a strong neural promoter in the 5'-upstream regulatory region.
“Recently, polymicrogyria restricted to the neocortical areas surrounding the Sylvian fissure including Broca’s area, the primary language area, was identified (Bae et al., 2014). The causative mutation is found in the GPR56 locus, but disrupts a noncoding element, which constitutes a strong neural promoter during development, in the 5’-upstream regulatory region of GPR56.”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Bae et al., 2014
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Self-citationComparative Anatomy of Marmoset and Mouse Cortex from Genomic Expression
Mashiko, H., Yoshida, A., Kikuchi, S. S., Niimi, K., Takahashi, E., Aruga, J., Okano, H., & Shimogori, T. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4788-11.2012 · Cited by 76 · see citing works
Self-citationQuantitative comparison and analysis of sulcal patterns using sulcal graph matching: A twin study
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GPR56 and TG2: Possible Roles in Suppression of Tumor Growth by the Microenvironment
Xu, L., & Hynes, R. O. (2007) · Cell Cycle · doi:10.4161/cc.6.2.3760 · Cited by 61 · see citing works
GPR56 Functions Together with α3β1 Integrin in Regulating Cerebral Cortical Development
Jeong, S., Luo, R., Singer, K., Giera, S., Kreidberg, J. A., Kiyozumi, D., Shimono, C., Sekiguchi, K., & Piao, X. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068781 · Cited by 50 · see citing works
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Golden, J. A., & Harding, B. N. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.118 · Cited by 16 · see citing works
Involvement of RFX proteins in transcriptional activation from a Ras-responsive enhancer element
Maijgren, S., Sur, I. K., Nilsson, M., et al. (2004) · Archives of Dermatological Research · doi:10.1007/s00403-004-0456-5 · Cited by 12 · see citing works
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Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning
Alipanahi, B., Delong, A., Weirauch, M. T., & Frey, B. J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3300 · Cited by 2,873 · see citing works
“A 15-bp deletion of a highly conserved segment deletes one of the binding sites, resulting in abnormal cortical development 40 .”
BackgroundHistory, Discovery, and Classification of lncRNAs
Jarroux, J., Morillon, A., & Pinskaya, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-5203-3_1 · Cited by 873 · see citing works
The Cellular and Molecular Landscapes of the Developing Human Central Nervous System
Silbereis, J. C., Pochareddy, S., Zhu, Y., Li, M., & Sestan, N. (2016) · Neuron · doi:10.1016/j.neuron.2015.12.008 · Cited by 818 · see citing works
Self-citationTaverna, E., Götz, M., & Huttner, W. Β. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155801 · Cited by 737 · see citing works
“Most intriguingly, acquisition of a multitude of new transcriptional start sites resulting in alternatively spliced transcripts in placental mammals allows region-specific regulation, affecting gyrification selectively in specific areas of the cerebral cortex (Bae et al. 2014, Singer et al. 2013).”
BackgroundBrain organoids: advances, applications and challenges
Qian, X., Song, H., & Ming, G.-L. (2019) · Development · doi:10.1242/dev.166074 · Cited by 724 · see citing works
“…ventral forebrain Guided Stationary floating culture Birey et al., 2017 Fused cerebral organoids Dorsal and ventral forebrain Guided Orbital shaker Bagley et al., 2017 Medial ganglionic eminence organoid Medial ganglionic eminence Guided Orbital shaker Xiang et al., 2017 Organoid grafts in mouse…”
BackgroundOn the growth and form of cortical convolutions
Tallinen, T., Chung, J. Y., Rousseau, F., Girard, N. J., Lefèvre, J., & Mahadevan, L. (2016) · Nature Physics · doi:10.1038/nphys3632 · Cited by 581 · see citing works
Whole-genome sequencing of quartet families with autism spectrum disorder
Yuen, R. K. C., Thiruvahindrapuram, B., Merico, D., Walker, S., Tammimies, K., Hoang, N., Chrysler, C., Nalpathamkalam, T., Pellecchia, G., Liu, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3792 · Cited by 514 · see citing works
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
Hamann, J., Aust, G., Araç, D., Engel, F. B., Formstone, C. J., Fredriksson, R., Hall, R. A., Harty, B. L., Kirchhoff, C., Knapp, B., et al. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009647 · Cited by 489 · see citing works
“Recently, a role for ADGRG1 (GPR56) in gyral patterning and, potentially, neocortex evolution has been described (Bae et al., 2014).”
BackgroundInfluentialSelf-citationInduction of Expansion and Folding in Human Cerebral Organoids
Li, Y., Muffat, J., Omer, A., Bosch, I., Lancaster, M. A., Sur, M., Gehrke, L., Knoblich, J. A., & Jaenisch, R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.017 · Cited by 436 · see citing works
“Differential regulation of NP proliferation may also contribute to human-specific cortical pattern formation (Bae et al., 2014).”
Gyrification from constrained cortical expansion
Tallinen, T., Chung, J. Y., Biggins, J. S., & Mahadevan, L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1406015111 · Cited by 418 · see citing works
“Indeed, the growing insight into regulatorymechanisms of neuronal proliferation andmigration (3, 4, 5, 6) implicates geneticmutations responsible for brain size (e.”
BackgroundMutations in Human Accelerated Regions Disrupt Cognition and Social Behavior
Doan, R. N., Bae, B.-I., Cubelos, B., Chang, C. Y., Hossain, A. A., Al-Saad, S., Mukaddes, N. M., Öner, Ö., Al‐Saffar, M., Balkhy, S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.071 · Cited by 342 · see citing works
“Unlike coding mutations, which are most often loss of function, regulatory mutations have the potential to be activating or inactivating of gene transcription in specific tissues (Bae et al., 2014; Weedon et al., 2014), typically due to gain or loss of essential transcription factor (TF) motifs.”
BackgroundSelf-citationStavropoulos, D. J., Merico, D., Jobling, R. K., Bowdin, S. C., Monfared, N., Thiruvahindrapuram, B., Nalpathamkalam, T., Pellecchia, G., Yuen, R. K. C., Szego, M. J., et al. (2016) · npj Genomic Medicine · doi:10.1038/npjgenmed.2015.12 · Cited by 366 · see citing works
Cerebral cortex expansion and folding: what have we learned?
Fernández, V., Llinares-Benadero, C., & Borrell, V. (2016) · The EMBO Journal · doi:10.15252/embj.201593701 · Cited by 357 · see citing works
“More recently, the evolution of active genomic enhancers was demonstrated with the analysis of the human GPR56 locus, mutated in malformations of cortical development including polymicrogyria (Bae et al , 2014).”
The mystery of language evolution
HAUSER, M. D., Yang, C. D., Berwick, R. C., Tattersall, I., Ryan, M. J., Watumull, J., Chomsky, N., & Lewontin, R. C. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00401 · Cited by 331 · see citing works
Boyd, J. L., Skove, S. L., Rouanet, J. P., Pilaz, L., Bepler, T., Gordân, R., Wray, G. A., & Silver, D. L. (2015) · Current Biology · doi:10.1016/j.cub.2015.01.041 · Cited by 282 · see citing works
“Yet to date, just a handful of genetic loci have been associated with human-specific brain traits [3, 5, 25], and none have been shown to functionally impact corticogenesis in an evolutionarily divergent fashion.”
BackgroundHistone Acetylome-wide Association Study of Autism Spectrum Disorder
Sun, W., Poschmann, J., Cruz-Herrera del Rosario, R., Parikshak, N. N., Hajan, H. S., Kumar, V., Ramasamy, R., Belgard, T. G., Elanggovan, B., Wong, C. C. Y., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.031 · Cited by 306 · see citing works
“Though there is no known genetic association of RFX TFs with ASD, members of this family play key roles in neurodevelopment (Benadiba et al., 2012; Bae et al., 2014), and our results raise the hypothesis that they could serve as mediators of diverse upstream causal factors.”
Deconstructing cortical folding: genetic, cellular and mechanical determinants
Llinares-Benadero, C., & Borrell, V. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0112-2 · Cited by 243 · see citing works
Long, K. R., Newland, B., Florio, M., Kalebic, N., Langen, B., Kolterer, A., Wimberger, P., & Huttner, W. B. (2018) · Neuron · doi:10.1016/j.neuron.2018.07.013 · Cited by 196 · see citing works
Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly
Romero, C. D. J., Bruder, C. E. G., Tomasello, U., Sanz‐Anquela, J. M., & Borrell, V. (2015) · The EMBO Journal · doi:10.15252/embj.201591176 · Cited by 173 · see citing works
“…changes at short-range in mRNA expression levels for several genes known to be key in cortical folding, such as EOMES, TRNP1, and GPR56 (Piao et al , 2004; Baala et al , 2007; Stahl et al , 2013; Bae et al , 2014) locally within the prospective prefrontal cortex and frontal lobe (Fig 8A –”
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex
Lui, J. H., Nowakowski, T. J., Pollen, A. A., Javaherian, A., Kriegstein, A. R., & Oldham, M. C. (2014) · Nature · doi:10.1038/nature13973 · Cited by 166 · see citing works
High-throughput functional comparison of promoter and enhancer activities
Nguyen, T. A., Jones, R. D., Snavely, A. R., Pfenning, A. R., Kirchner, R., Hemberg, M., & Gray, J. M. (2016) · Genome Research · doi:10.1101/gr.204834.116 · Cited by 146 · see citing works
“6B; Maijgren et al. 2004; Bae et al. 2014).”
Genomic Perspectives of Transcriptional Regulation in Forebrain Development
Nord, A. S., Pattabiraman, K., Visel, A., & Rubenstein, J. L. R. (2015) · Neuron · doi:10.1016/j.neuron.2014.11.011 · Cited by 152 · see citing works
“In a recent example of a large effect noncoding variant with severe phenotypic consequences in the brain, a short deletion in regulatory sequence was identified in subjects exhibiting gyral abnormalities (Bae et al., 2014).”
Rash, B. G., Duque, A., Morozov, Y. M., Arellano, J. I., Micali, N., & Rakic, P. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1822169116 · Cited by 156 · see citing works
“, lissencephaly and polymicrogyria (12, 13).”
Giera, S., Deng, Y., Luo, R., Ackerman, S. D., Mogha, A., Monk, K. R., Ying, Y., Jeong, S., Makinodan, M., Bialas, A. R., et al. (2015) · Nature Communications · doi:10.1038/ncomms7121 · Cited by 141 · see citing works
“A recent study shows that GPR56 regulates neural stem cell proliferation 21 , but its role in oligodendrocyte development remains unknown.”
InfluentialSelf-citationComprehensive comparative analysis of 5′-end RNA-sequencing methods
Adiconis, X., Haber, A. L., Simmons, S., Levy‐Moonshine, A., Ji, Z., Busby, M., Shi, X., Jacques, J., Lancaster, M. A., Pan, J. Q., et al. (2018) · Nature Methods · doi:10.1038/s41592-018-0014-2 · Cited by 121 · see citing works
“…TSS, which has been shown to be the highest expressed TSS in fetal human brain and required for normal human embryonic cerebral cortical development 38 , was used more frequently in the fetal frontal lobe, in vitro neurons, and brain organoids, but not in the adult frontal lobe, in which T3 was…”
Genetic Changes Shaping the Human Brain
Bae, B.-I., Jayaraman, D., & Walsh, C. A. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.035 · Cited by 135 · see citing works
Self-citationThe Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells
Chang, G.-W., Hsiao, C., Peng, Y.-M., Braga, F. A. V., Kragten, N. A. M., Remmerswaal, E. B. M., van de Garde, M. D. B., Straussberg, R., König, G. M., Kostenis, E., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.053 · Cited by 121 · see citing works
“Studies in other cell types have implicated roles of GPR56 in the generation and maintenance of the hematopoietic stem cell pool, cortical development, male fertility, muscle hypertrophy, and melanoma tumor growth and progression (Ackerman et al., 2015; Bae et al., 2014; Chen et al., 2010; Giera et al., 2015; Piao et…”
BackgroundA restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels
Martínez‐Martínez, M. Á., Romero, C. D. J., Fernández, V., Cárdenas, A., Götz, M., & Borrell, V. (2016) · Nature Communications · doi:10.1038/ncomms11812 · Cited by 129 · see citing works
Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains
Salzman, G., Ackerman, S. D., Ding, C., Koide, A., Leon, K., Luo, R., Stoveken, H. M., Fernandez, C., Tall, G. G., Piao, X., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.08.022 · Cited by 128 · see citing works
Self-citationGenetics and mechanisms leading to human cortical malformations
Romero, D. M., Bahi‐Buisson, N., & Francis, F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.031 · Cited by 126 · see citing works
Mapping the molecular and cellular complexity of cortical malformations
Klingler, E., Francis, F., Jabaudon, D., & Cappello, S. (2021) · Science · doi:10.1126/science.aba4517 · Cited by 122 · see citing works
“Sources of complexity in cortical malformations Cortical malformations have a broad range of clinical expression, including seizures, intellectual disabilities, autistic features, failure to reach developmental milestones, and nonneurological comorbidities (e.g., dysmorphic Klingler et al., Science 371, eaba4517 (2021…”
BackgroundInfluentialSchöneberg, T., & Liebscher, I. (2020) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000011 · Cited by 127 · see citing works
“An interesting case of a 15-bp deletion in the regulatory region of GPR56 (ADGRG1) led to local disruption of GPR56 expression, resulting in restricted polymicrogyria limited to the cortex surrounding the Sylvian fissure (Bae et al., 2014).”
BackgroundNamba, T., & Huttner, W. Β. (2016) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.256 · Cited by 115 · see citing works
“Changes in noncoding genomic regions are also important for brain evolution.(109,110) A recent study has identified a novel human-accelerated regulatory enhancer called HARE5.”
BackgroundAdhesion G protein-coupled receptors in nervous system development and disease
Langenhan, T., Piao, X., & Monk, K. R. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.86 · Cited by 115 · see citing works
Self-citationExome sequencing and whole genome sequencing for the detection of copy number variation
Hehir‐Kwa, J. Y., Pfundt, R., & Veltman, J. A. (2015) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2015.1053467 · Cited by 109 · see citing works
“4 kb de novo deletion 283 kb 5¢ of FOXL2, which is known to be the disease-causing gene of BPES [74] as well as a 15 bp deletion disrupting a cis-regulatory element of GPR56 known to be involved in cortical development [75].”
BackgroundCharacterization of the human RFX transcription factor family by regulatory and target gene analysis
Sugiaman‐Trapman, D., Vitezic, M., Jouhilahti, E., Mathelier, A., Lauter, G., Misra, S., Daub, C. O., Kere, J., & Swoboda, P. (2018) · BMC Genomics · doi:10.1186/s12864-018-4564-6 · Cited by 102 · see citing works
“…example, one might expect male sterility to be associated with mutations in testis specific RFX1 – 4 gene isoforms, or with dys-regulation of testis specific RFX target genes (e.g. GPR56 [86], ALMS1 [87] and RFX1 ), or with the role upstream RFX regulators (e.g. ESR1 [88, 89]) play in ciliogenesis.”
BackgroundNeuronal migration disorders: Focus on the cytoskeleton and epilepsy
Stouffer, M. A., Golden, J. A., & Francis, F. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.08.003 · Cited by 114 · see citing works
Human-specific genomic signatures of neocortical expansion
Florio, M., Borrell, V., & Huttner, W. Β. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.11.004 · Cited by 96 · see citing works
Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance
Bertolini, J. A., Favaro, R., Zhu, Y., Pagin, M., Ngan, C. Y., Wong, C., Tjong, H., Vermunt, M. W., Martynoga, B., Barone, C., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.02.004 · Cited by 96 · see citing works
Sulcal pits and patterns in developing human brains
Im, K., & Grant, P. E. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.03.057 · Cited by 95 · see citing works
“It also clearly defined the cortical areas affected by a noncoding mutation in the GPR56 gene in polymicrogyria (Bae et al., 2014).”
BackgroundSelf-citationEnabling research with human embryonic and fetal tissue resources
Gerrelli, D., Lisgo, S., Copp, A. J., & Lindsay, S. (2015) · Development · doi:10.1242/dev.122820 · Cited by 89 · see citing works
“Advances in high-throughput sequencing technologies have opened the door to large-scale cross-species comparisons that are highlighting differences in transcript sequence, alternative splicing, expression level and regulation between humans and model organisms (Cotney et al., 2013; Bae et al., 2014).”
Self-citationCoevolution of radial glial cells and the cerebral cortex
Romero, C. D. J., & Borrell, V. (2015) · Glia · doi:10.1002/glia.22827 · Cited by 96 · see citing works
“…there exist species-specific variations in the GPR56 regulatory regions that drive gene expression in distinct patterns in the developing neocortex, strongly suggesting this may be a mechanism contributing to define the species-specific pattern of cortical folding across mammals (Bae et al., 2014).”
BackgroundShaping the brain: The emergence of cortical structure and folding
Akula, S. K., Exposito-Alonso, D., & Walsh, C. A. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.11.004 · Cited by 97 · see citing works
Self-citationThe atoms of neural computation
Marcus, G., Marblestone, A. H., & Dean, T. (2014) · Science · doi:10.1126/science.1261661 · Cited by 80 · see citing works
“Seemingly slight molecular differences, such as the alternative splicing of GPR56, may have profound consequences in human development and evolution, for example by selectively altering stem cell proliferation and gyral patterning in the vicinity of Broca’s area (Bae et al., 2014).”
BackgroundBrain Transcriptome Databases: A User's Guide
Keil, J. M., Qalieh, A., & Kwan, K. Y. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1930-17.2018 · Cited by 74 · see citing works
Cellular and Molecular Mechanisms Linking Human Cortical Development and Evolution
Libé-Philippot, B., & Vanderhaeghen, P. (2021) · Annual Review of Genetics · doi:10.1146/annurev-genet-071719-020705 · Cited by 78 · see citing works
Perenthaler, E., Yousefi, S., Niggl, E., & Barakat, T. S. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00352 · Cited by 71 · see citing works
GPR56/ADGRG1 regulates development and maintenance of peripheral myelin
Ackerman, S. D., Luo, R., Poitelon, Y., Mogha, A., Harty, B. L., D’Rozario, M., Sanchez, N., Lakkaraju, A. K., Gamble, P. G., Li, J., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20161714 · Cited by 68 · see citing works
“, 2016), and GPR56 is a known regulator of cell division (Wu et al., 2013; Bae et al., 2014; Ackerman et al., 2015; Giera et al., 2015); thus, we first tested if Gpr56 mutant SCs were less proliferative than WT.”
BackgroundSelf-citationAdhesion G Protein-Coupled Receptors as Drug Targets for Neurological Diseases
Folts, C. J., Giera, S., Li, T., & Piao, X. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.02.003 · Cited by 70 · see citing works
Self-citationOrphan G Protein Coupled Receptors in Affective Disorders
Watkins, L. R., & Orlandi, C. (2020) · Genes · doi:10.3390/genes11060694 · Cited by 67 · see citing works
“Overall, ADGRG1 was concluded to be a potential antidepressant target since it is involved in various biological functions relevant to the pathophysiology of depression: neurogenesis, oligodendrocyte development, progenitor cell migration in brain, and myelin repair [109,110,119].”
BackgroundIncreasing the sensitivity of clinical exome sequencing through improved filtration strategy
Shamseldin, H. E., Maddirevula, S., Faqeih, E., Ibrahim, N., Hashem, M., Shaheen, R., & Alkuraya, F. S. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.155 · Cited by 72 · see citing works
Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets
Langenhan, T. (2019) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13223 · Cited by 65 · see citing works
GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma
Moreno, M., Pedrosa, L., Paré, L., Pineda, E., Bejarano, L., Martínez, J., Balasubramaniyan, V., Ezhilarasan, R., Kallarackal, N., Kim, S.-H., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.083 · Cited by 74 · see citing works
“GPR56 is an adhesion GPCR with a prominent role in NSC and OPC proliferation and differentiation (Ackerman et al., 2015; Bae et al., 2014; Giera et al., 2015) and is highly expressed in PN and CL GBMs (Figure 1A).”
BackgroundSelf-citationZhu, B., Luo, R., Jin, P., Li, T., Oak, H. C., Giera, S., Monk, K. R., Lak, P., Shoichet, B. K., & Piao, X. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008234 · Cited by 62 · see citing works
Self-citationLoss of PCLO function underlies pontocerebellar hypoplasia type III
Ahmed, M. Y., Chioza, B. A., Rajab, A., Schmitz‐Abe, K., Al‐Khayat, A., Al-Turki, S., Baple, E. L., Patton, M. A., Al‐Memar, A., Hurles, M. E., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001523 · Cited by 66 · see citing works
“Messenger RNA sequencing data from human fetal (9 weeks postconception) cerebral cortex was obtained as previously described.(7)”
MethodSelf-citationGPR56/ADGRG1 is associated with response to antidepressant treatment
Belzeaux-R, R., Gorgievski, V., Fiori, L. M., López, J. P., Grenier, J., Lin, R., Nagy, C., Ibrahim, E. C., Gascon, E., Courtet, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15423-5 · Cited by 65 · see citing works
A Comprehensive Mutagenesis Screen of the Adhesion GPCR Latrophilin-1/ADGRL1
Nazarko, O. V., Kibrom, A., Winkler, J., Leon, K., Stoveken, H. M., Salzman, G., Merdas, K., Lu, Y., Narkhede, P., Tall, G. G., et al. (2018) · iScience · doi:10.1016/j.isci.2018.04.019 · Cited by 60 · see citing works
Dunn, H. A., Orlandi, C., & Martemyanov, K. A. (2019) · Pharmacological Reviews · doi:10.1124/pr.119.018044 · Cited by 66 · see citing works
“…presence of four alternative splicing isoforms in the ADGRG1 ectodomain, two of which include large deletions, further implicates a multilayered regulatory function that may differentiate ADGRG1 activation mechanisms beyond collagen III – modulated signaling via the PLL domain (Bae et al., 2014).”
BackgroundFerent, J., Zaidi, D., & Francis, F. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.578341 · Cited by 64 · see citing works
The role of GPR56/ADGRG1 in health and disease
Singh, A. K., & Lin, H. (2021) · Biomedical Journal · doi:10.1016/j.bj.2021.04.012 · Cited by 60 · see citing works
Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium
Niaudet, C., Hofmann, J. J., Mäe, M. A., Jung, B., Gaengel, K., Vanlandewijck, M., Ekvärn, E., Salvado, M. D., Mehlem, A., Sayegh, S. A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137949 · Cited by 55 · see citing works
“Mutations in the human gene, GPR56, cause a malformation of the cerebral cortex known as bilateral frontoparietal polymicrogyria [13].”
BackgroundZhang, S., Chatterjee, T., Godoy, C., Wu, L., Liu, Q. J., & Carmon, K. S. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0436 · Cited by 54 · see citing works
Epilepsy and malformations of cortical development
Kuzniecky, R. (2015) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000175 · Cited by 49 · see citing works
Morphological and functional aspects of progenitors perturbed in cortical malformations
Bizzotto, S., & Francis, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00030 · Cited by 52 · see citing works
“The Frontiers in Cellular Neuroscience www.frontiersin.org February 2015 | Volume 9 | Article 30 | 3 Table 2 | Specific genes mouse mutants.”
BackgroundInfluentialUnderstanding cadherin EGF LAG seven‐pass G‐type receptors
Wang, X., Zhang, D., Xu, Z., Ma, M., Wang, W., Li, L., Han, X., Huo, Y., Yu, X., & Sun, J. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12955 · Cited by 52 · see citing works
Genetic basis of functional variability in adhesion G protein-coupled receptors
Knierim, A. B., Röthe, J., Çakır, M. V., Lede, V., Wilde, C., Liebscher, I., Thor, D., & Schöneberg, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-46265-x · Cited by 49 · see citing works
RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans
Shamseldin, H. E., Alazami, A. M., Manning, M. A., Hashem, A., Caluseiu, O., Tabarki, B. M., Esplin, E. D., Schelley, S. L., Innes, A. M., Parboosingh, J. S., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.10.012 · Cited by 50 · see citing works
Jin, G., Sakitani, K., Wang, H., Jin, Y., Dubeykovskiy, A. N., Worthley, D. L., Tailor, Y. H., & Wang, T. C. (2017) · Oncotarget · doi:10.18632/oncotarget.16506 · Cited by 48 · see citing works
Neuronal migration and disorders – an update
Francis, F., & Cappello, S. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.10.002 · Cited by 48 · see citing works
Modeling autism in non‐human primates: Opportunities and challenges
Zhao, H., Jiang, Y., & Zhang, Y. (2018) · Autism Research · doi:10.1002/aur.1945 · Cited by 50 · see citing works
“GPR56 regulates lateral cortical development in gyrencephalic mammals [Bae et al., 2014].”
Bilemjian, V., Vlaming, M. R., Freile, J. Á., Huls, G. A., de Bruyn, M., & Bremer, E. (2022) · Cancers · doi:10.3390/cancers14133164 · Cited by 35 · see citing works
“GPR56 is an adhesion G-protein-coupled receptor with an array of functions, ranging from cortical development [20,21], anti-depressant response [22], hematopoietic development [23], to tumor cell adhesion and progression [24–26].”
BackgroundVitobello, A., Mazel, B., Lelianova, V. G., Zangrandi, A., Petitto, E., Suckling, J., Salpietro, V., Meyer, R., Elbracht, M., Kurth, I., et al. (2022) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.06.011 · Cited by 46 · see citing works
The Role of Transposable Elements of the Human Genome in Neuronal Function and Pathology
Chesnokova, E., Beletskiy, A., & Kolosov, P. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105847 · Cited by 48 · see citing works
A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration
O’Neill, A. C., Kyrousi, C., Klaus, J., Leventer, R. J., Kirk, E. P., Fry, A. E., Pilz, D. T., Morgan, T., Jenkins, Z. A., Drukker, M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.029 · Cited by 48 · see citing works
“A consequence of these rapid, expansive cortical evolutionary events, particularly in humans, could be a trade-off that has rendered the brain susceptible to certain neurodevelopmental and neuropsychiatric conditions (Bae et al., 2014; Doan et al., 2016; Bershteyn et al., 2017).”
BackgroundNucleocytoplasmic transport of the RNA-binding protein CELF2 regulates neural stem cell fates
MacPherson, M. J., Erickson, S. L., Kopp, D., Wen, P., Aghanoori, M., Kedia, S., Burns, K. M. L., Vitobello, A., Mau‐Them, F. T., Thomas, Q., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109226 · Cited by 43 · see citing works
Im, K., Guimarães, A. M. L., Kim, Y., Cottrill, E. J., Gagoski, B. A., Rollins, C. K., Ortinau, C. M., Yang, E., & Grant, P. E. (2017) · American Journal of Neuroradiology · doi:10.3174/ajnr.a5217 · Cited by 42 · see citing works
Self-citationTang, J., Fan, Y., Li, H., Xiang, Q., Zhang, D., Li, Z., He, Y., Liao, Y., Wang, Y., He, F., et al. (2017) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2017.05.005 · Cited by 43 · see citing works
“Mutations in the nongenic (Bae et al., 2014), noncoding RNA (Kwon et al., 2013), and large CNV regions (Liu et al., 2002; Xu et al., 2008; CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium, 2017) may play important roles in the development of neuropsychiatric disorders…”
BackgroundZhang, Y., Si, Y., Ma, N., & Mei, J. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.06.139 · Cited by 43 · see citing works
Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders
Sun, Y., Liu, F.-X., Fan, C., Wang, Y.-S., Song, L.-J., Fang, Z., Han, R., Wang, Z.-H., Wang, X., Yang, Z.-Y., et al. (2020) · BMC Medical Genomics · doi:10.1186/s12920-021-00948-5 · Cited by 36 · see citing works
“Several studies have demonstrated the 81 advantages of WGS for variant detection [11-14].”
Lin, H., Ma, C., Zhuang, X., Liu, S., Liu, D., Zhang, M., Lu, Y., Zhou, G., Zhang, C., Wang, T., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.09.007 · Cited by 47 · see citing works
Silver, D. L. (2015) · BioEssays · doi:10.1002/bies.201500108 · Cited by 41 · see citing works
“[40] demonstrated that a 15 nt deletion within the 50 promoter of human GPR56, a G protein coupled receptor, causes polymicrogyria in the cortical area controlling language.”
BackgroundA molecular model for neurodevelopmental disorders
Gigek, C. O., Chen, E., Ota, V., Maussion, G., Peng, H., Vaillancourt, K., Diallo, A., López, J. P., Crapper, L., Vasuta, C., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.56 · Cited by 38 · see citing works
Disorganized Patterns of Sulcal Position in Fetal Brains with Agenesis of Corpus Callosum
Tarui, T., Madan, N., Farhat, N., Kitano, R., Tanritanir, A. C., Graham, G., Gagoski, B. A., Craig, A. K., Rollins, C. K., Ortinau, C. M., et al. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx191 · Cited by 40 · see citing works
Self-citationShimada, I. S., Somatilaka, B. N., Hwang, S., Anderson, A. G., Shelton, J. M., Rajaram, V., Konopka, G., & Mukhopadhyay, S. (2019) · Developmental Biology · doi:10.1016/j.ydbio.2019.03.011 · Cited by 34 · see citing works
“Rather, increased folding of the cortex might be related to IPC populations, as seen in mice with transgenic overexpression of human Gpr56 that regulates gyral patterning (Bae et al., 2014).”
BackgroundCharting the protomap of the human telencephalon
Clowry, G. J., Alzu’bi, A., Harkin, L. F., Sarma, S., Kerwin, J. M., & Lindsay, S. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.08.033 · Cited by 33 · see citing works
Setting the clock of neural progenitor cells during mammalian corticogenesis
Koo, B., Lee, K., Ming, G., Yoon, K., & Song, H. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.05.013 · Cited by 37 · see citing works
“For example, human G protein-coupled receptor 56 ( GPR56 ) has 15 promoters that enhance NPC proliferation in the human cortex [113].”
BackgroundTammimies, K., Bieder, A., Lauter, G., Sugiaman‐Trapman, D., Torchet, R., Hokkanen, M., Burghoorn, J., Ċastrén, E., Kere, J., Tapia‐Páez, I., et al. (2016) · The FASEB Journal · doi:10.1096/fj.201500124rr · Cited by 32 · see citing works
Chatterjee, T., Zhang, S., Posey, T. A., Jacob, J., Wu, L., Yu, W., Francisco, L. E., Liu, Q. J., & Carmon, K. S. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100261 · Cited by 28 · see citing works
Metabolic regulation and glucose sensitivity of cortical radial glial cells
Rash, B. G., Micali, N., Huttner, A. J., Morozov, Y. M., Horváth, T. L., & RAKIC, P. T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808066115 · Cited by 36 · see citing works
“Likewise, neuronal displacement involving failed or improper migration can be caused by defects in RGC function triggered by a variety of genetic mutations and can lead to neurodevelopmental disorders of the cerebral cortex with consequent lifelong cognitive impairments (12, 13).”
BackgroundKordon, S. P., Dutka, P., Adamska, J. M., Bandekar, S. J., Leon, K., Erramilli, S. K., Adams, B., Li, J., Kossiakoff, A. A., & Araç, D. (2023) · Nature Communications · doi:10.1038/s41467-023-36312-7 · Cited by 31 · see citing works
Matsunaga, E., Nambu, S., Oka, M., & Iriki, A. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.032 · Cited by 27 · see citing works
Maffioli, E., Schulte, C., Nonnis, S., Scalvini, F. G., Piazzoni, C., Lenardi, C., Negri, A. L., Milani, P., & Tedeschi, G. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00417 · Cited by 29 · see citing works
“…Um and Ko, 2013; Sarhan et al., 2016), Gpr56 (Piao et al., 2004; Iguchi et al., 2008; Gong et al., 2010; Shen et al., 2012; Jeong et al., 2013; Bae et al., 2014), ROCK (Yamaguchi et al., 2001; Loudon et al., 2006; Lee et al., 2010; Schulte et al., 2010), GFRA1 (Cao et al., 2008; Marks et al.,…”
Role of ADGRG1/GPR56 in Tumor Progression
Ng, K., Chen, T., Stacey, M. A., & Lin, H. (2021) · Cells · doi:10.3390/cells10123352 · Cited by 33 · see citing works
“protein isoforms remain to be fully investigated [27,28].”
BackgroundNew functions and signaling mechanisms for the class of adhesion G protein–coupled receptors
Liebscher, I., Ackley, B. D., Araç, D., Ariestanti, D. M., Aust, G., Bae, B.-I., Bista, B. R., Bridges, J. P., Duman, J. G., Engel, F. B., et al. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12580 · Cited by 30 · see citing works
Self-citationCatalogue of inherited disorders found among the Irish Traveller population
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Enhancing our brains: Genomic mechanisms underlying cortical evolution
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The Activation and Signaling Mechanisms of GPR56/ADGRG1 in Melanoma Cell
Huang, K., & Lin, H. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00304 · Cited by 29 · see citing works
“More recently, it was further shown that regional cerebral cortical patterning was tightly regulated by the GPR56 expression levels controlled in part by a specific cis-regulatory non-exonic element and generation of multiple alternative splicing forms (30).”
BackgroundRole of intracortical neuropil growth in the gyrification of the primate cerebral cortex
Rash, B. G., Arellano, J. I., Duque, A., & RAKIC, P. T. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210967120 · Cited by 30 · see citing works
“The protomap and radial unit model of cortical development is thus supported by the most advanced genetic methods (57) and can be extended to the principle of gyrification via these maturational characteristics.”
Kawase, S., Kuwako, K.-I., Imai, T., et al. (2014) · Stem Cells and Development · doi:10.1089/scd.2014.0219 · Cited by 32 · see citing works
Self-citationCancer Cell Mechanics: Adhesion G Protein-coupled Receptors in Action?
Scholz, N. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00059 · Cited by 32 · see citing works
“Thus, attachment and size-dependent tensility of NTFs may be critical for mechanosensing through aGPCRs.”
BackgroundInfluential
- Authors
- Bae, B.-I., Tietjen, I., Atabay, K. D., Evrony, G. D., Johnson, M. B., Asare, E., Wang, P. P., Murayama, A. Y., Im, K., Lisgo, S. N., Overman, L., Šestan, N., Chang, B. S., Barkovich, A. J., Grant, P. E., Topçu, M., Politsky, J., Okano, H., Piao, X., & Walsh, C. A.
- Affiliations
- Broad Institute (US)
- Keio University (JP)
- Boston Children's Hospital (US)
- Centre for Life (GB)
- Yale University (US)
- Beth Israel Deaconess Medical Center (US)
- University of California, San Francisco (US)
- Hacettepe University (TR)
- Augusta University (US)
- Corresponding author
- Bae, Byoung-Il
- Tietjen, Ian
- Politsky, Jeffrey
- Walsh, Christopher A.
- ORCID
- Venue
- Science
- Published
- 2014-02-14
- Volume
- 343
- Issue
- 6172
- Pages
- 764-768
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4480613
- OpenAlex
- W1979208523
- Semantic Scholar
- ab78a1227d69c6090e8a819cd5935b59848b1f92
- Cited by
- 229
- References
- 40
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 10 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 44 · 2019: 21 · 2018: 20 · 2017: 18 · 2016: 21 · 2015: 26 · 2014: 14
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Hacettepe University Institutional Repository (hacettepe.edu.tr) (submittedVersion, other-oa)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (GR082557)
- Medical Research Council (MC_PC_15004)
- National Institute of Mental Health (U01MH081896)
- National Institute of Neurological Disorders and Stroke (R01NS035129)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275200900011C, P30HD018655, N01-HD-90011)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- GPR56, alternative splicing, alternative promoters, cortical development, Broca's area, Sylvian fissure, RFX transcription factors, G protein-coupled receptors, cortical progenitor cells, stem cell proliferation, neocortex evolution, laterality
- MeSH terms
- Animals, Base Sequence, Cats, Cerebral Cortex, Biological Evolution, Frontal Lobe, Haplotypes, Humans, Molecular Sequence Data, Pedigree, Promoter Regions, Genetic, Genetic Variation, Sequence Deletion, Alternative Splicing, Codon, Nonsense, Body Patterning, Receptors, G-Protein-Coupled, Cell Proliferation, Mice, Neural Stem Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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