{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:55:52Z","timestamp":1775883352945,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,14]]},"group-title":"Developmental Biology","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Primary cilia play a pivotal role in cellular signaling and development and disruptions in ciliary form and\/or function leads to human ciliopathies. Here, we examine the role of\n                  <jats:italic>Ttc21b<\/jats:italic>\n                  , a key component of the intraflagellar transport-A complex, in mouse forebrain development using a\n                  <jats:italic>Ttc21b<\/jats:italic>\n                  <jats:sup>\n                    <jats:italic>alien<\/jats:italic>\n                  <\/jats:sup>\n                  null allele. Our findings reveal significant microcephaly in homozygous mutants is caused by disrupted neural progenitor proliferation and differentiation. Histological and immunohistochemical analyses show an enlarged ventricular zone and reduced cortical plate thickness, accompanied by altered mitotic spindle angles, suggesting defects in symmetric versus asymmetric cell divisions. Despite low\n                  <jats:italic>Ttc21b<\/jats:italic>\n                  expression in the forebrain epithelium, early embryonic expression patterns imply that perdurant TTC21B protein may underlie these phenotypes. Progenitor proliferation kinetics were disrupted, with fewer cells re-entering the cell cycle, correlating with reduced TBR2-positive intermediate progenitors and altered neurogenesis dynamics. Neuronal processes in the cortical plate were significantly shortened, suggesting cytoskeletal defects specific to terminal differentiation stages. Our findings support a model where early\n                  <jats:italic>Ttc21b<\/jats:italic>\n                  expression in precursors destined for the forebrain is critical for sustaining later neural progenitor proliferation and differentiation. These results advance our understanding of primary cilia in cortical development and provide a framework for exploring cytoskeletal contributions to ciliopathies.\n                <\/jats:p>","DOI":"10.1101\/2025.01.14.632919","type":"posted-content","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T21:25:12Z","timestamp":1736889912000},"source":"Crossref","is-referenced-by-count":0,"title":["Perdurant TTC21B protein in the early mouse embryo is required for proper forebrain neural progenitor proliferation"],"prefix":"10.64898","author":[{"given":"Rebekah","family":"Niewoehner","sequence":"first","affiliation":[{"name":"Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Paulding","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus","family":"Leal","sequence":"additional","affiliation":[{"name":"Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-6806","authenticated-orcid":false,"given":"Rolf W.","family":"Stottmann","sequence":"additional","affiliation":[{"name":"Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041021260575000_2025.01.14.632919v1.1","unstructured":"Alberts B. 1994. 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Primary Cilia Influence Progenitor Function during Cortical Development. Cells 11.","DOI":"10.3390\/cells11182895"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.01.14.632919","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T04:26:15Z","timestamp":1775881575000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.01.14.632919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":25,"URL":"https:\/\/doi.org\/10.1101\/2025.01.14.632919","relation":{},"subject":[],"published":{"date-parts":[[2025,1,14]]},"subtype":"preprint"}}