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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:p>\n                    Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into the cortex where they make connections with locally produced excitatory glutamatergic neurons. Cortical function critically depends on the number of cINs, which is also key to establishing the appropriate inhibitory\/excitatory balance. The final number of cINs is determined during a postnatal period of programmed cell death (PCD) when ~40% of the young cINs are eliminated. Previous work shows that the loss of clustered gamma protocadherins (Pcdhgs), but not of genes in the\n                    <jats:italic>Pcdha<\/jats:italic>\n                    or\n                    <jats:italic>Pcdhb<\/jats:italic>\n                    clusters, dramatically increased BAX-dependent cIN PCD. Here, we show that\n                    <jats:italic>Pcdh\u03b3C4<\/jats:italic>\n                    is highly expressed in cINs of the mouse cortex and that this expression increases during PCD. The sole deletion of the Pcdh\u03b3C4 isoform, but not of the other 21 isoforms in the\n                    <jats:italic>Pcdhg<\/jats:italic>\n                    gene cluster, increased cIN PCD. Viral expression of the\n                    <jats:italic>Pcdh\u03b3C4,<\/jats:italic>\n                    in cIN lacking the function of the entire\n                    <jats:italic>Pcdhg<\/jats:italic>\n                    cluster, rescued most of these cells from cell death. We conclude that\n                    <jats:italic>Pcdh\u03b3C4<\/jats:italic>\n                    plays a critical role in regulating the survival of cINs during their normal period of PCD. This highlights how a single isoform of the\n                    <jats:italic>Pcdhg<\/jats:italic>\n                    cluster, which has been linked to human neurodevelopmental disorders, is essential to adjust cIN cell numbers during cortical development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2313596120","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T15:00:21Z","timestamp":1706540421000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["The clustered gamma protocadherin Pcdh\u03b3C4 isoform regulates cortical interneuron programmed cell death in the mouse cortex"],"prefix":"10.1073","volume":"121","author":[{"given":"Walter R. Mancia","family":"Leon","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4599-3005","authenticated-orcid":false,"given":"David M.","family":"Steffen","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143"},{"name":"Department of Biology, The University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona R.","family":"Dale-Huang","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rakela","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnar","family":"Breevoort","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Romero-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea R.","family":"Hasenstaub","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143"},{"name":"Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1546-5831","authenticated-orcid":false,"given":"Michael P.","family":"Stryker","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of California, San Francisco, San Francisco, CA 94143"},{"name":"Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Biology, The University of Iowa, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-8925","authenticated-orcid":false,"given":"Arturo","family":"Alvarez-Buylla","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143"},{"name":"Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01581-2"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.14.030191.002321"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.677"},{"key":"e_1_3_4_4_2","first-page":"4","article-title":"The multiple life of nerve growth factor: Tribute to Rita Levi-Montalcini (1909\u20132012)","volume":"30","author":"Aloe L.","year":"2013","unstructured":"L. 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