Molecular signatures and lineage diversification of neurogenic and gliogenic radial glia in the gyrencephalic ferret cortex

Molecular signatures and lineage diversification of neurogenic and gliogenic radial glia in the gyrencephalic ferret cortex | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Molecular signatures and lineage diversification of neurogenic and gliogenic radial glia in the gyrencephalic ferret cortex Zhengang Yang, Jialin Li, Feihong Yang, Weiwei Li, Tongye Fu, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8062841/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Human exceptional cognition stems from evolutionarily derived cortical adaptations that drive expansive neurogenesis. In this study, we employ the gyrencephalic ferret model to systematically characterize the molecular profiles and lineage dynamics of cortical radial glia (RGs). By applying scRNA-Seq to ferret and human cortices, we identify conserved regulatory programs underlying cortical neurogenesis and gliogenesis in mammals. Through integrated scRNA-Seq, BrdU labeling, and immunohistochemical approaches, we show that, similar to their human counterparts, ferret cortical outer radial glia (oRGs), exhibit enhanced ERK and PKA signaling. ERK and PKA act in a mutually reinforcing manner to boost oRG self-renewal and neurogenesis, while inhibiting gliogenesis and prolonging the neurogenic period. Furthermore, we identify regional specialization within cortical gliogenic RGs: YAP/TAZ activation drives ventricular zone truncated radial glia (tRGs) toward ependymal glial fate in medial cortex, whereas SHH signaling instructs lateral cortical tRGs to generate tripotential intermediate progenitor cells, which serve as a shared source of astrocytes, oligodendrocytes, and cortically-derived olfactory bulb interneurons. Our findings support a model in which mammalian cortical neurogenesis, gliogenesis, and evolutionary expansion are co-regulated through an integrated signaling network orchestrated by ERK, PKA, YAP/TAZ, and SHH. This network relies on a precisely balanced interplay of mutual inhibition among these pathways to ensure proper developmental outcomes. Biological sciences/Developmental biology/Differentiation Biological sciences/Neuroscience/Development of the nervous system cortical development cortical evolution gyrencephalic ferret neurogenesis gliogenesis ERK PKA YAP SHH signaling outer radial glia Full Text Additional Declarations There is NO Competing Interest. Supplementary Files FerretSupplementaryMaterials.pdf Supplementary Figurs Tables.zip Supplementary table1-3 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8062841","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":543458265,"identity":"e54e1e86-6c12-4da4-953b-52e94260d483","order_by":0,"name":"Zhengang 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