Protocadherin γC4 promotes neuronal survival in the mouse retina through its variable cytoplasmic domain

Protocadherin γC4 promotes neuronal survival in the mouse retina through its variable cytoplasmic domain | 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 Research Article Protocadherin γC4 promotes neuronal survival in the mouse retina through its variable cytoplasmic domain Cathy M. McLeod, Hannah G. Lanthier, Garrett R. Nitschke, Samjhana Bhandari, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6206977/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Molecular Neurobiology → Version 1 posted 23 You are reading this latest preprint version Abstract Developmental apoptosis is an important mechanism for the formation of functional neural circuits. Distinct neuronal subtypes undergo apoptosis to a greater or lesser extent during development, although how this is regulated at the cell type level is unknown. The clustered Protocadherins (cPcdhs) are ~ 60 homophilic cell adhesion molecules expressed from three contiguous gene clusters, which together encode the a-, b-, and g-Pcdh families. Only one cPcdh isoform, gC4, is essential for survival in the mouse, given its role in attenuating the extent of developmental neuronal apoptosis. However, there is also evidence that other isoforms contribute to neuronal survival. Here we focused on amacrine cell types in the mouse retina, using a series of genetic models to ascertain that gC4 alone accounts for the pro-survival function of the g-Pcdhs, and that neuronal subtype dependence on g-Pcdhs for survival correlates with expression of this single isoform. To test which domains of the protein were essential for this function, we employed a rescue approach with in vitro live cell imaging, finding that the unique variable cytoplasmic domain of gC4–not its adhesive extracellular cadherin repeats–is necessary and sufficient promote neuronal survival. apoptosis γ-Protocadherin neural development retina mouse Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementalvideos.zip Cite Share Download PDF Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Molecular Neurobiology → Version 1 posted Editorial decision: Revision requested 21 Apr, 2025 Reviews received at journal 18 Apr, 2025 Reviews received at journal 16 Apr, 2025 Reviews received at journal 16 Apr, 2025 Reviewers agreed at journal 08 Apr, 2025 Reviewers agreed at journal 07 Apr, 2025 Reviewers agreed at journal 07 Apr, 2025 Reviewers agreed at journal 07 Apr, 2025 Reviewers agreed at journal 06 Apr, 2025 Reviewers agreed at journal 06 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers invited by journal 01 Apr, 2025 Editor assigned by journal 22 Mar, 2025 Submission checks completed at journal 22 Mar, 2025 First submitted to journal 11 Mar, 2025 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-6206977","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":431028856,"identity":"fa30687a-16af-42b3-aad8-a63f6370299c","order_by":0,"name":"Cathy M. 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