22q11 deletion selectively alters progenitor states and projection neuron identities in the developing cerebral cortex

22q11 deletion selectively alters progenitor states and projection neuron identities in the developing cerebral 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 22q11 deletion selectively alters progenitor states and projection neuron identities in the developing cerebral cortex Anthony-Samuel LaMantia, Shah Rukh, Daniel Meechan, Connor Siggins, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6531749/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 Heterozygous deletion of multiple contiguous genes associated with 22q11.2 Deletion Syndrome (22q11DS), a developmental disorder with significant risk for autistic spectrum disorder (ASD) and schizophrenia (Scz), selectively compromises neurogenic capacities of a temporally distinct cohort of cerebral cortical basal progenitors (bPs), prefiguring diminished frequency, divergent times of origin, positions, and identities of a subset of Layer 2/3 projection neuron (PN) progeny in the LgDel 22q11DS mouse model. LgDel bPs express 24/28 contiguous murine 22q11 gene orthologues at diminished levels; in parallel, cell cycle kinetics, modes of division, gene expression levels, and DNA methylation states are aberrant in LgDel bPs but not their apical progenitor precursors. Accordingly, targeted disruption of bP proliferative and transcriptional states selectively alters Layer 2/3 PN identities and frequencies, prefiguring atypical association cortico-cortical connections and behavioral deficits associated with ASD and Scz pathology in a mouse model of 22q11DS. Biological sciences/Neuroscience/Development of the nervous system/Neural progenitors Biological sciences/Neuroscience/Diseases of the nervous system/Developmental disorders Biological sciences/Neuroscience/Diseases of the nervous system/Schizophrenia Biological sciences/Genetics/Neurodevelopmental disorders/Autism spectrum disorders Full Text Additional Declarations There is NO Competing Interest. All animal experiments were performed under protocols 22-208 and 23-001, reviewed and approved by the Virginia Tech Institutional Animal Use and Care Committee (IACUC). Supplementary Files Rukhetal042525SUPPFIGTABLE.pdf Supplemental Figures, Tables, and Legends 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6531749","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":451233737,"identity":"7e9dfa17-0e79-4193-84bc-0477931842e6","order_by":0,"name":"Anthony-Samuel 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