ArticleProceedings of the National Academy of Sciences of the United States of America2022
A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia expansion and neocortical folding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- A transcriptional atlas of gyrification reveals dynamic spatio-temporal gene expression in the developing ferret cortex.Brain structure & function · 2026Article
- Molecular signatures and lineage diversification of neurogenic and gliogenic radial glia in the gyrencephalic ferret cortex.Communications biology · 2026Article
- Integrated ERK-PKA-YAP/TAZ-SHH Signaling Orchestrates Cortical Radial Glia Identity and Lineage Diversification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-Nucleus Transcriptomics of the Nucleus Accumbens Reveals Cell-Type-Specific Dysregulation in Adolescent Macaques with Depressive-Like Behaviors.Neuroscience bulletin · 2025Article
- The Principle of Cortical Development and Evolution.Neuroscience bulletin · 2025Review
- Hedgehog signaling controls astral microtubules and mitotic spindle orientation in neural progenitors and iPSCs.Frontiers in cell and developmental biology · 2025Article
- The Control of Cortical Folding: Multiple Mechanisms, Multiple Models.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Embryonic mouse medial neocortex as a model system for studying the radial glial scaffold in fetal human neocortex.Journal of neural transmission (Vienna, Austria : 1996) · 2023Article
- A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia expansion and neocortical folding.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
The neocortex, the center for higher brain function, first emerged in mammals and has become massively expanded and folded in humans, constituting almost half the volume of the human brain. Primary microcephaly, a developmental disorder in which the brain is smaller than normal at birth, results mainly from there being fewer neurons in the neocortex because of defects in neural progenitor cells (NPCs). Outer radial glia (oRGs), NPCs that are abundant in gyrencephalic species but rare in lissencephalic species, are thought to play key roles in the expansion and folding of the neocortex. However, how oRGs expand, whether they are necessary for neocortical folding, and whether defects in oRGs cause microcephaly remain important questions in the study of brain development, evolution, and disease. Here, we show that oRG expansion in mice, ferrets, and human cerebral organoids requires cyclin-dependent kinase 6 (CDK6), the mutation of which causes primary microcephaly via an unknown mechanism. In a mouse model in which increased Hedgehog signaling expands oRGs and intermediate progenitor cells and induces neocortical folding, CDK6 loss selectively decreased oRGs and abolished neocortical folding. Remarkably, this function of CDK6 in oRG expansion did not require its kinase activity, was not shared by the highly similar CDK4 and CDK2, and was disrupted by the mutation causing microcephaly. Therefore, our results indicate that CDK6 is conserved to promote oRG expansion, that oRGs are necessary for neocortical folding, and that defects in oRG expansion may cause primary microcephaly.
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