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.
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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
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- 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
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