Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex
Open accessAbstract
Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signalling pathways. By analysing differential gene co-expression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG in human, but not mouse, corticogenesis. We also show that the expression domain of PDGFRβ, the cognate receptor for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD-PDGFRβ signalling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant PDGFD or ectopic expression of constitutively active PDGFRβ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD-PDGFRβ signalling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Lui et al. (2014) revealed a number of genes enriched in either mouse or human radial glia cells.
“In particular, by analyzing differential gene co-expression relationships between fetal human and mouse neocortial proliferative zones and cells, Lui and colleagues (Lui et al., 2014) revealed a number of genes that were enriched in either mouse or human RG cells (Figure 4C).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Lui et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A General Framework for Weighted Gene Co-Expression Network Analysis
Zhang, B., & Horvath, S. (2005) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1128 · Cited by 5,684 · see citing works
Specification of Cerebral Cortical Areas
Rakic, P. (1988) · Science · doi:10.1126/science.3291116 · Cited by 3,127 · see citing works
An anatomically comprehensive atlas of the adult human brain transcriptome
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., et al. (2012) · Nature · doi:10.1038/nature11405 · Cited by 3,083 · see citing works
Spatio-temporal transcriptome of the human brain
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., et al. (2011) · Nature · doi:10.1038/nature10523 · Cited by 2,084 · see citing works
Evolution of the neocortex: a perspective from developmental biology
Rakic, P. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2719 · Cited by 1,565 · see citing works
Neurogenic radial glia in the outer subventricular zone of human neocortex
Hansen, D. V., Lui, J. H., Parker, P. R. L., & Kriegstein, A. R. (2010) · Nature · doi:10.1038/nature08845 · Cited by 1,388 · see citing works
Self-citationDevelopment and Evolution of the Human Neocortex
Lui, J. H., Hansen, D. V., & Kriegstein, A. R. (2011) · Cell · doi:10.1016/j.cell.2011.06.030 · Cited by 1,342 · see citing works
Self-citationTranscriptional landscape of the prenatal human brain
Miller, J. A., Ding, S.-L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., et al. (2014) · Nature · doi:10.1038/nature13185 · Cited by 1,325 · see citing works
Golub, T. R., Barker, G. F., Lovett, M., & Gilliland, D. G. (1994) · Cell · doi:10.1016/0092-8674(94)90322-0 · Cited by 1,154 · see citing works
Geometric Interpretation of Gene Coexpression Network Analysis
Horvath, S., & Dong, J. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000117 · Cited by 849 · see citing works
Modeling transformations of neurodevelopmental sequences across mammalian species
Workman, A. D., Charvet, C. J., Clancy, B., Darlington, R. B., & Finlay, B. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.5746-12.2013 · Cited by 833 · see citing works
OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling
Fietz, S. A., Kelava, I., Vogt, J., Wilsch-Bräuninger, M., Stenzel, D., Fish, J. L., Corbeil, D., Riehn, A., Distler, W., Nitsch, R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2553 · Cited by 830 · see citing works
Functional organization of the transcriptome in human brain
Oldham, M. C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., & Geschwind, D. H. (2008) · Nature Neuroscience · doi:10.1038/nn.2207 · Cited by 752 · see citing works
Self-citationSmart, I. H. M. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.1.37 · Cited by 687 · see citing works
A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo
Diez-Roux, G., Banfi, S., Sultan, M., Geffers, L., Anand, S., Rozado, D., Magen, A., Canidio, E., Pagani, M., Peluso, I., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000582 · Cited by 638 · see citing works
Johnson, M. B., Kawasawa, Y. I., Mason, C. E., Krsnik, Ž., Coppola, G., Bogdanović, D., Geschwind, D. H., Mane, S. M., State, M. W., & Šestan, N. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.027 · Cited by 603 · see citing works
Conservation and evolution of gene coexpression networks in human and chimpanzee brains
Oldham, M. C., Horvath, S., & Geschwind, D. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605938103 · Cited by 566 · see citing works
PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor
Bergsten, E., Uutela, M., Li, X., et al. (2001) · Nature Cell Biology · doi:10.1038/35074588 · Cited by 563 · see citing works
Human-specific loss of regulatory DNA and the evolution of human-specific traits
McLean, C. Y., Reno, P. L., Pollen, A. A., Bassan, A. I., Capellini, T. D., Guenther, C., Indjeian, V. B., Lim, X., Menke, D. B., Schaar, B. T., et al. (2011) · Nature · doi:10.1038/nature09774 · Cited by 535 · see citing works
Self-citationCortical Evolution: Judge the Brain by Its Cover
Geschwind, D. H., & Rakic, P. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.045 · Cited by 519 · see citing works
PDGF-D, a new protease-activated growth factor
LaRochelle, W. J., Jeffers, M., McDonald, W. F., et al. (2001) · Nature Cell Biology · doi:10.1038/35074593 · Cited by 403 · see citing works
Fietz, S. A., Lachmann, R., Brandl, H., Kircher, M., Samusik, N., Schröder, R., Lakshmanaperumal, N., Henry, I., Vogt, J., Riehn, A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209647109 · Cited by 337 · see citing works
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., et al. (2014) · Science · doi:10.1126/science.1244392 · Cited by 229 · see citing works
Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis
Kawaguchi, A., Ikawa, T., Kasukawa, T., Ueda, H. R., Kurimoto, K., Saitou, M., & Matsuzaki, F. (2008) · Development · doi:10.1242/dev.022616 · Cited by 193 · see citing works
Antiangiogenic and Antitumor Activity of a Selective PDGFR Tyrosine Kinase Inhibitor, CP-673,451
Roberts, W. G., Whalen, P. M., Söderström, E., Moraski, G. C., Lyssikatos, J. P., Wang, H. F., Cooper, B. A., Baker, D. A., Savage, D. M., Dalvie, D., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.957.65.3 · Cited by 134 · see citing works
Emerging roles of PDGF-D signaling pathway in tumor development and progression
Wang, Z. P., Ahmad, A., Li, Y., Kong, D., Azmi, A. S., Banerjee, S., & Sarkar, F. H. (2010) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2010.04.003 · Cited by 119 · see citing works
Pinto, L., Mader, M., Irmler, M., Gentilini, M., Santoni, F., Drechsel, D., Blum, R., Stahl, R., Bulfone, A., Malatesta, P., et al. (2008) · Molecular and cellular neurosciences · doi:10.1016/j.mcn.2008.01.012 · Cited by 105 · see citing works
Magnusson, P. U., Looman, C., Åhgren, A., Wu, Y. L., Claesson, L., & Heuchel, R. L. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000282198.60701.94 · Cited by 78 · see citing works
Ajioka, I., Maeda, T., & Nakajima, K. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04544.x · Cited by 22 · see citing works
(2013) · Oxford University Press eBooks · doi:10.1093/med/9780199855452.001.0001 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [9]Oldham MC Transcriptomics: from differential expression to coexpression The OMICs: Applications in Neuroscienc Coppola G Oxford University Press Oxford 2014 1 85
Cited by
Sorted by citations
Assembly of functionally integrated human forebrain spheroids
Birey, F., Andersen, J., Makinson, C. D., Islam, S., Wei, W., Huber, N., Fan, H. C., Metzler, K. R. C., Panagiotakos, G., Thom, N., et al. (2017) · Nature · doi:10.1038/nature22330 · Cited by 1,365 · see citing works
Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex
Nowakowski, T. J., Bhaduri, A., Pollen, A. A., Alvarado, B., Mostajo-Radji, M. A., Di Lullo, E., Haeussler, M., Sandoval-Espinosa, C., Liu, S. J., Velmeshev, D., et al. (2017) · Science · doi:10.1126/science.aap8809 · Cited by 964 · see citing works
Self-citationMolecular Identity of Human Outer Radial Glia during Cortical Development
Pollen, A. A., Nowakowski, T. J., Chen, J., Retallack, H., Sandoval-Espinosa, C., Nicholas, C. R., Shuga, J., Liu, S. J., Oldham, M. C., Diaz, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.004 · Cited by 908 · see citing works
Self-citationAdvancing the understanding of autism disease mechanisms through genetics
de la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016) · Nature Medicine · doi:10.1038/nm.4071 · Cited by 827 · 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
Human-specific gene <i>ARHGAP11B</i> promotes basal progenitor amplification and neocortex expansion
Florio, M., Albert, M., Taverna, E., Namba, T., Brandl, H., Lewitus, E., Haffner, C., Sykes, A., Wong, F. K., Peters, J., et al. (2015) · Science · doi:10.1126/science.aaa1975 · Cited by 632 · see citing works
Evolution of the Human Nervous System Function, Structure, and Development
Sousa, A. M. M., Meyer, K. A., Santpere, G., Gulden, F. O., & Sestan, N. (2017) · Cell · doi:10.1016/j.cell.2017.06.036 · Cited by 517 · see citing works
Induction 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
Otani, T., Marchetto, M. C., Gage, F. H., Simons, B. D., & Livesey, F. J. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.03.003 · Cited by 353 · see citing works
The outer subventricular zone and primate-specific cortical complexification
Dehay, C., Kennedy, H., & Kosik, K. S. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.060 · Cited by 314 · see citing works
Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex
Johnson, M. B., Wang, P. P., Atabay, K. D., Murphy, E. A., Doan, R. N., Hecht, J. L., & Walsh, C. A. (2015) · Nature Neuroscience · doi:10.1038/nn.3980 · Cited by 288 · see citing works
Kelley, K. W., Nakao-Inoue, H., Molofsky, A. V., & Oldham, M. C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0216-z · Cited by 198 · see citing works
Self-citationDevelopmental mechanisms underlying the evolution of human cortical circuits
Vanderhaeghen, P., & Polleux, F. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00675-z · Cited by 173 · 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
Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells
Suzuki, I. K., & Vanderhaeghen, P. (2015) · Development · doi:10.1242/dev.120568 · Cited by 110 · 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
Diversity of Cortical Interneurons in Primates: The Role of the Dorsal Proliferative Niche
Radonjić, N. V., Ayoub, A. E., Memi, F., Yu, X., Maroof, A., Jakovcevski, I., Anderson, S. A., Rakic, P., & Zecevic, N. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.11.026 · Cited by 74 · see citing works
Oxygen levels regulate the development of human cortical radial glia cells
Ortega, J. A., Sirois, C. L., Memi, F., Glidden, N., & Zecevic, N. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw194 · Cited by 37 · see citing works
CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types
Nelms, B. D., Waldron, L., Barrera, L. A., Weflen, A. W., Goettel, J. A., Guo, G., Montgomery, R. K., Neutra, M. R., Breault, D. T., Snapper, S. B., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1062-5 · Cited by 24 · see citing works
- Authors
- Lui, J. H., Nowakowski, T. J., Pollen, A. A., Javaherian, A., Kriegstein, A. R., & Oldham, M. C.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Kriegstein, Arnold R.
- Oldham, Michael C.
- ORCID
- Venue
- Nature
- Published
- 2014-11
- Volume
- 515
- Issue
- 7526
- Pages
- 264-268
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4231536
- OpenAlex
- W2092682926
- Cited by
- 166
- References
- 30
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 11 · 2023: 13 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 17 · 2018: 17 · 2017: 15 · 2016: 24 · 2015: 17 · 2014: 2
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- University of California, Los Angeles
- National Institute of Neurological Disorders and Stroke (R01NS072630, R01NS075998, R01NS021223)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- radial glia, PDGF-D, PDGFRβ, cortical development, cell cycle progression, human-mouse comparison, gene co-expression, neurogenesis, brain slice culture, gene expression profiling, brain evolution
- MeSH terms
- Animals, Cell Cycle, Humans, Lymphokines, Neuroglia, Platelet-Derived Growth Factor, Transcription, Genetic, Signal Transduction, Neocortex, Receptor, Platelet-Derived Growth Factor beta, Gene Expression Profiling, Cell Proliferation, 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
