{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T17:45:16Z","timestamp":1776534316277,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,15]]},"group-title":"Developmental Biology","reference-count":16,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD102492"],"award-info":[{"award-number":["R01HD102492"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32GM139787"],"award-info":[{"award-number":["T32GM139787"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Proper forebrain development relies on precise spatial and temporal control of early neural stem cell (NSC) proliferation and later neurogenesis. Brain malformations can arise when these processes are defective. Joubert Syndrome (JS) is a neurodevelopmental disorder that is diagnosed by a mid-hindbrain malformation, but often includes forebrain defects such as microcephaly, which are less understood. One gene recently linked to Joubert Syndrome with microcephaly is\n                  <jats:italic>Togaram1<\/jats:italic>\n                  , which encodes a TOG domain microtubule binding protein shown to affect primary cilia. In the embryonic dorsal forebrain, NSCs have primary cilia on their apical membranes that play a role in regulating proliferation and neurogenesis, but how they do this is not well understood. Here we investigate the role of\n                  <jats:italic>Togaram1<\/jats:italic>\n                  in mammalian forebrain development using a mouse knockout. We find that\n                  <jats:italic>Togaram1<\/jats:italic>\n                  is crucial for forebrain size, thickness, and morphology. In particular, knockout forebrains have sporadic indentations of the lateral ventricles, and the neuronal layer is thin with gaps and heterotopias. The dorsal forebrain NSCs have increased proliferation and apoptosis. Finally, the primary cilia of\n                  <jats:italic>Togaram1<\/jats:italic>\n                  knockout NSCs have abnormal morphology and function. This study begins to elucidate the role of\n                  <jats:italic>Togaram1<\/jats:italic>\n                  in forebrain morphogenesis and the involvement of NSC primary cilia in forebrain malformations.\n                <\/jats:p>","DOI":"10.64898\/2026.04.13.717734","type":"posted-content","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:00:20Z","timestamp":1776250820000},"source":"Crossref","is-referenced-by-count":0,"title":["Microtubule binding protein Togaram1 is required for proper development of mammalian forebrain and neural primary cilia"],"prefix":"10.64898","author":[{"given":"Clarissa Q.","family":"Nassar","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA"},{"name":"Cell and Developmental Biology Graduate Program, University of Virginia School of Medicine, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savera J.","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelle D.","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041810300934000_2026.04.13.717734v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-07009-0"},{"key":"2026041810300934000_2026.04.13.717734v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13010021"},{"key":"2026041810300934000_2026.04.13.717734v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01475-0"},{"key":"2026041810300934000_2026.04.13.717734v1.4","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E15-08-0603"},{"key":"2026041810300934000_2026.04.13.717734v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03670-5"},{"key":"2026041810300934000_2026.04.13.717734v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2004.00819.x"},{"key":"2026041810300934000_2026.04.13.717734v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03775-x"},{"key":"2026041810300934000_2026.04.13.717734v1.8","doi-asserted-by":"crossref","unstructured":"Latour, B. L. , Van De Weghe, J. C. , Rusterholz, T. D. S. , Letteboer, S. J. F. , Gomez, A. , Shaheen, R. , Gesemann, M. , Karamzade, A. , Asadollahi, M. , Barroso-Gil, M. , Chitre, M. , Grout, M. E. , van Reeuwijk, J. , van Beersum, S. E. C. , Miller, C. V. , Dempsey, J. C. , Morsy, H. , Bamshad, M. J. , Nickerson, D. A. , \u2026 Doherty, D. (2020). Dysfunction of the ciliary ARMC9\/TOGARAM1 protein module causes Joubert syndrome. The Journal of Clinical Investigation.","DOI":"10.1172\/JCI131656"},{"key":"2026041810300934000_2026.04.13.717734v1.9","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201804141"},{"key":"2026041810300934000_2026.04.13.717734v1.10","doi-asserted-by":"publisher","DOI":"10.1007\/s40778-021-00193-7"},{"key":"2026041810300934000_2026.04.13.717734v1.11","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-106833"},{"key":"2026041810300934000_2026.04.13.717734v1.12","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21-09-0472"},{"key":"2026041810300934000_2026.04.13.717734v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-025-01483-y"},{"key":"2026041810300934000_2026.04.13.717734v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.07.014"},{"key":"2026041810300934000_2026.04.13.717734v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2025.11.002"},{"key":"2026041810300934000_2026.04.13.717734v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2024.100363"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.13.717734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T17:30:18Z","timestamp":1776533418000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.13.717734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":16,"URL":"https:\/\/doi.org\/10.64898\/2026.04.13.717734","relation":{},"subject":[],"published":{"date-parts":[[2026,4,15]]},"subtype":"preprint"}}