G Protein-Coupled Receptor-Dependent Development of Human Frontal Cortex
Abstract
The mammalian cerebral cortex is characterized by complex patterns of anatomical and functional areas that differ markedly between species, but the molecular basis for this functional subdivision is largely unknown. Here, we show that mutations in GPR56 , which encodes an orphan G protein–coupled receptor (GPCR) with a large extracellular domain, cause a human brain cortical malformation called bilateral frontoparietal polymicrogyria (BFPP). BFPP is characterized by disorganized cortical lamination that is most severe in frontal cortex. Our data suggest that GPCR signaling plays an essential role in regional development of human cerebral cortex.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Mutations in GPR56 coding sequences cause polymicrogyria in most of the neocortex.
“Mutations in the coding sequences cause polymicrogyria (‘too many small gyri’) in most of the neocortex (Piao et al., 2004).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Piao et al., 2004
GPR56 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).”
From Evolutionarily Dynamic Alternative Splicing of <i>GPR56</i> Regulates Regional Cerebral Cortical Patterning (2014) · cites this paper as [7]
Cites
Specification of Cerebral Cortical Areas
Rakic, P. (1988) · Science · doi:10.1126/science.3291116 · Cited by 3,127 · see citing works
Mode of cell migration to the superficial layers of fetal monkey neocortex
Rakic, P. (1972) · Journal of Comparative Neurology · doi:10.1002/cne.901450105 · Cited by 2,170 · see citing works
Molecular tinkering of G protein‐coupled receptors: an evolutionary success
Bockaert, J., & Pin, J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.7.1723 · Cited by 1,548 · see citing works
Interneuron Migration from Basal Forebrain to Neocortex: Dependence on <i>Dlx</i> Genes
Anderson, S. A., Eisenstat, D. D., Shi, L., & Rubenstein, J. L. R. (1997) · Science · doi:10.1126/science.278.5337.474 · Cited by 1,462 · see citing works
Tbr1 regulates differentiation of the preplate and layer 6
Hevner, R. F., Shi, L., Justice, N., Hsueh, Y.-P., Sheng, M., Smiga, S., Bulfone, A., Goffinet, A. M., Campagnoni, A. T., & Rubenstein, J. L. R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00211-2 · Cited by 857 · see citing works
Origin of GABAergic neurons in the human neocortex
Letinić, K., Zoncu, R., & RAKIC, P. T. (2002) · Nature · doi:10.1038/nature00779 · Cited by 718 · see citing works
Neocortex Patterning by the Secreted Signaling Molecule FGF8
Fukuchi-Shimogori, T., & Grove, E. (2001) · Science · doi:10.1126/science.1064252 · Cited by 707 · see citing works
Widespread Dispersion of Neuronal Clones Across Functional Regions of the Cerebral Cortex
Walsh, C. A., & Cepko, C. L. (1992) · Science · doi:10.1126/science.1734520 · Cited by 613 · see citing works
Self-citationRegulation of Area Identity in the Mammalian Neocortex by Emx2 and Pax6
Bishop, K. M., Goudreau, G., & O’Leary, D. D. M. (2000) · Science · doi:10.1126/science.288.5464.344 · Cited by 575 · see citing works
Luskin, M. B., Pearlman, A., & Sanes, J. (1988) · Neuron · doi:10.1016/0896-6273(88)90163-8 · Cited by 554 · see citing works
Do cortical areas emerge from a protocortex?
O'Leary, D. D. M. (1989) · Trends in Neurosciences · doi:10.1016/0166-2236(89)90080-5 · Cited by 536 · see citing works
Clonally Related Cortical Cells Show Several Migration Patterns
Walsh, C. A., & Cepko, C. L. (1988) · Science · doi:10.1126/science.3137660 · Cited by 509 · see citing works
Self-citationYoung neurons from medial ganglionic eminence disperse in adult and embryonic brain
Wichterle, H., Garcia-Verdugo, J. M., Herrera, D. G., & Alvarez-Buylla, A. (1999) · Nature Neuroscience · doi:10.1038/8131 · Cited by 506 · see citing works
Congenital bilateral perisylvian syndrome: study of 31 patients
Kuzniecky, R. (1993) · The Lancet · doi:10.1016/0140-6736(93)90363-l · Cited by 325 · see citing works
From hematopoiesis to neuropoiesis: Evidence of overlapping genetic programs
Terskikh, A. V., Easterday, M. C., Li, L., Hood, L., Kornblum, H. I., Geschwind, D. H., & Weissman, I. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131200898 · Cited by 288 · see citing works
Area identity shifts in the early cerebral cortex of Emx2−/− mutant mice
Mallamaci, A., Muzio, L., Chan, C. H., Parnavelas, J. G., & Boncinelli, E. (2000) · Nature Neuroscience · doi:10.1038/76630 · Cited by 253 · see citing works
Tan, S., Kalloniatis, M., Sturm, K. S., Tam, P., Reese, B. E., & Faulkner-Jones, B. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80539-5 · Cited by 238 · see citing works
LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors
Stacey, M. A., Lin, H., Gordon, S., & McKnight, A. J. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01583-8 · Cited by 194 · see citing works
Bilateral parasagittal parietooccipital polymicrogyria and epilepsy
Guerrini, R., Dubeau, F., Dulac, O., et al. (1997) · Annals of Neurology · doi:10.1002/ana.410410112 · Cited by 157 · see citing works
Krasnoperov, V. G., Lu, Y., Buryanovsky, L. N., Neubert, T. A., Ichtchenko, K., & Petrenko, A. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206415200 · Cited by 152 · see citing works
Chang, B. S., Piao, X., Bodell, A., Basel‐Vanagaite, L., Straussberg, R., Dobyns, W. B., Qasrawi, B., Winter, R. M., Innes, A. M., Voït, T., et al. (2003) · Annals of Neurology · doi:10.1002/ana.10520 · Cited by 134 · see citing works
Self-citationA Locus for Bilateral Perisylvian Polymicrogyria Maps to Xq28
Villard, L., Nguyen, K., Cardoso, C., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/339433 · Cited by 122 · see citing works
There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini
Fredriksson, R., Gloriam, D. E. I., Höglund, P. J., Lagerström, M. C., & Schiöth, H. B. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00026-3 · Cited by 120 · see citing works
An Autosomal Recessive Form of Bilateral Frontoparietal Polymicrogyria Maps to Chromosome 16q12.2-21
Piao, X., Basel‐Vanagaite, L., Straussberg, R., Grant, P. E., Pugh, E., Doheny, K. F., Doan, B. Q., Hong, S. E., Shugart, Y. Y., & Walsh, C. A. (2002) · The American Journal of Human Genetics · doi:10.1086/339552 · Cited by 120 · see citing works
Self-citationLiu, Q., Dwyer, N. D., & O’Leary, D. D. M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-20-07682.2000 · Cited by 118 · see citing works
Molecular Gradients and Compartments in the Embryonic Primate Cerebral Cortex
Donoghue, M. J. (1999) · Cerebral Cortex · doi:10.1093/cercor/9.6.586 · Cited by 115 · see citing works
GPR56, a Novel Secretin-like Human G-Protein-Coupled Receptor Gene
Liu, M., Parker, R. M. C., Darby, K., Eyre, H. J., Copeland, N. G., Crawford, J., Gilbert, D. J., Sutherland, G. R., Jenkins, N. A., & Herzog, H. (1999) · Genomics · doi:10.1006/geno.1998.5644 · Cited by 91 · see citing works
Antoine, J.-C. G., Cinotti, L., Tilikete, C., Bouhour, F., Camdessanch�, J. P., Confavreux, C., Vighetto, A., Renault‐Mannel, V., Michel, D., & Honnorat, J. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200007)48:1 · Cited by 86 · see citing works
Unlayered polymicrogyria : structural and developmental aspects
Ferrer, I., & Catal�, I. (1991) · Anatomy and Embryology · doi:10.1007/bf01236058 · Cited by 62 · see citing works
Bilateral frontoparietal polymicrogyria and epilepsy
Sztriha, L., & Nork, M. (2000) · Pediatric Neurology · doi:10.1016/s0887-8994(99)00142-3 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regional Brain Changes in Aging Healthy Adults: General Trends, Individual Differences and Modifiers
Raz, N., Lindenberger, U., Rodrigue, K. M., Kennedy, K. M., Head, D., Williamson, A., Dahle, C., Gerstorf, D., & Acker, J. D. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhi044 · Cited by 2,875 · see citing works
Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness
Panizzon, M. S., Fennema-Notestine, C., Eyler, L. T., Jernigan, T. L., Prom-Wormley, E., Neale, M., Jacobson, K., Lyons, M. J., Grant, M. D., Franz, C. E., et al. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp026 · Cited by 1,304 · see citing works
Gosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307 · see citing works
Guerrini, R. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68182-8 · Cited by 848 · see citing works
Identifying autism loci and genes by tracing recent shared ancestry
Morrow, E. M., Yoo, S.-Y., Flavell, S. W., Kim, T.-K., Lin, Y., Hill, R. S., Mukaddes, N. M., Balkhy, S., Gascon, G., Hashmi, A., et al. (2008) · Science · doi:10.1126/science.1157657 · Cited by 737 · see citing works
Self-citationThe origin of mind: Evolution of brain, cognition, and general intelligence.
Geary, D. C. (2005) · doi:10.1037/10871-000 · Cited by 551 · see citing works
G1 Phase Regulation, Area-Specific Cell Cycle Control, and Cytoarchitectonics in the Primate Cortex
Lukaszewicz, A., Savatier, P., Cortay, V., Giroud, P., Huissoud, C., Berland, M., Kennedy, H., & Dehay, C. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.032 · Cited by 315 · see citing works
Luo, R., Jeong, S.-J., Jin, Z., Strokes, N., Li, S., & Piao, X. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104821108 · Cited by 290 · see citing works
Self-citationTemporal Specification and Bilaterality of Human Neocortical Topographic Gene Expression
Pletikos, M., Sousa, A. M. M., Sedmak, G., Meyer, K. A., Zhu, Y., Cheng, F., Li, M., Kawasawa, Y. I., & Šestan, N. (2014) · Neuron · doi:10.1016/j.neuron.2013.11.018 · Cited by 228 · see citing works
GPR56 Regulates Pial Basement Membrane Integrity and Cortical Lamination
Li, S., Jin, Z., Koirala, S., Bu, L., Xu, L., Hynes, R. O., Walsh, C. A., Corfas, G., & Piao, X. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0853-08.2008 · Cited by 241 · see citing works
Self-citationBae, 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., et al. (2014) · Science · doi:10.1126/science.1244392 · Cited by 229 · see citing works
Self-citationEmerging roles of neural stem cells in cerebral cortex development and evolution
Borrell, V., & Reillo, I. (2012) · Developmental Neurobiology · doi:10.1002/dneu.22013 · Cited by 185 · see citing works
Bahi-Buisson, N., Poirier, K., Boddaert, N., Fallet-Bianco, C., Specchio, N., Bertini, E., Caglayan, O., Lascelles, K., Elie, C., Rambaud, J., et al. (2010) · Brain · doi:10.1093/brain/awq259 · Cited by 144 · see citing works
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-citationGiera, S., Luo, R., Ying, Y., Ackerman, S. D., Jeong, S.-J., Stoveken, H. M., Folts, C. J., Welsh, C. A., Tall, G. G., Stevens, B., et al. (2018) · eLife · doi:10.7554/elife.33385 · Cited by 145 · see citing works
Self-citationPrefrontal Executive Function Syndromes in Children
Powell, K. B., & Voeller, K. K. S. (2004) · Journal of Child Neurology · doi:10.1177/08830738040190100801 · Cited by 137 · see citing works
Alcántara, S., Pozas, E., Ibañez, C. F., & Soriano, E. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhi128 · Cited by 71 · see citing works
The G protein-coupled receptor GPRC5B contributes to neurogenesis in the developing mouse neocortex
Kurabayashi, N., Nguyen, M. D., & Sanada, K. (2013) · Development · doi:10.1242/dev.099754 · Cited by 46 · see citing works
Arreguin, A. J., & Colognato, H. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00118 · Cited by 39 · see citing works
Jeong, S., Luo, R., Li, S., Strokes, N., & Piao, X. (2012) · Journal of Comparative Neurology · doi:10.1002/cne.23076 · Cited by 36 · see citing works
Self-citation
- Authors
- Piao, X., Hill, R. S., Bodell, A., Chang, B. S., Basel-Vanagaite, L., Straussberg, R., Dobyns, W. B., Qasrawi, B., Winter, R. M., Innes, A. M., Voit, T., Ross, M. E., Michaud, J. L., Déscarie, J.-C., Barkovich, A. J., & Walsh, C. A.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
- Corresponding author
- Winter, Robin M.
- Walsh, Christopher A.
- ORCID
- Venue
- Science
- Published
- 2004-03-26
- Volume
- 303
- Issue
- 5666
- Pages
- 2033-2036
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2130955385
- Cited by
- 517
- References
- 30
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 26 · 2023: 15 · 2022: 28 · 2021: 26 · 2020: 27 · 2019: 20 · 2018: 20 · 2017: 20 · 2016: 32 · 2015: 29 · 2014: 27 · 2013: 23 · 2012: 25
- FWCI
- 21.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K08NS045762, R37NS035129)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 07466)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- GPR56, orphan G protein-coupled receptor, malformations of cortical development, cortical lamination, G protein-coupled receptor signaling, human brain development
- MeSH terms
- Animals, Cerebral Cortex, Cerebral Ventricles, Biological Evolution, Female, Frontal Lobe, Humans, Ligands, Male, Neurons, Parietal Lobe, Stem Cells, Signal Transduction, Frameshift Mutation, Antisense Elements (Genetics), Sequence Deletion, Sequence Homology, Amino Acid, Body Patterning, Amino Acid Substitution, Mutation, Missense, Gene Order, Receptors, G-Protein-Coupled, Mice
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
