{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:57:20Z","timestamp":1775894240716,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,13]]},"group-title":"Developmental Biology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"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":[[2025,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Orofacial clefts, including cleft palate (CP), are among the most common types of birth defects. CP specifically, results from a failure of palatal shelf fusion during development. Previous studies have shown that mutations in\n                  <jats:italic>RhoA GTPase Activating Protein 29<\/jats:italic>\n                  (\n                  <jats:italic>ARHGAP29)<\/jats:italic>\n                  are linked to CP, yet the role and tissue-specific requirements for ARHGAP29 during palatogenesis remain unknown. Here, we use tissue-specific deletion of\n                  <jats:italic>Arhgap29<\/jats:italic>\n                  in mice to provide the first direct evidence that ARHGAP29 is essential for proper palatal elevation and fusion. We demonstrate that ectodermal conditional loss of\n                  <jats:italic>Arhgap29<\/jats:italic>\n                  induces a significant delay in the fusion of palatal shelves at embryonic (E) day 14.5 and an incomplete yet significantly penetrant cleft palate at E18.5 \u2013 neither of which are observed when\n                  <jats:italic>Arhgap29<\/jats:italic>\n                  is lost later in development using K14-Cre. Phenotypic analyses of palatal shelves at E14.5 reveal a disorganized and thicker epithelium at the tip of the shelves. Loss of\n                  <jats:italic>Arhgap29<\/jats:italic>\n                  increases palate epithelial cell area and upregulates alpha-smooth muscle actin and phospho-myosin regulatory light chain implicating cell morphology and contractility as drivers of CP.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary statement<\/jats:title>\n                  <jats:p>\n                    This study in mice is the first direct evidence that ARHGAP29 is essential for proper palatal elevation and fusion. Loss of\n                    <jats:italic>Arhgap29<\/jats:italic>\n                    alters oral epithelial morphology and upregulates contractility proteins.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.11.642653","type":"posted-content","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T22:15:17Z","timestamp":1741904117000},"source":"Crossref","is-referenced-by-count":1,"title":["The ectodermal loss of ARHGAP29 alters epithelial morphology and organization and disrupts murine palatal development"],"prefix":"10.64898","author":[{"given":"Emily","family":"Adelizzi","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA"},{"name":"Interdisciplinary graduate program in genetics, The University of Iowa, Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey","family":"Rhea","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Campbell","family":"Mitvalsky","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Pek","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany","family":"Doolittle","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Dunnwald","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA"},{"name":"Interdisciplinary graduate program in genetics, The University of Iowa, Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041100154524000_2025.03.11.642653v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"2026041100154524000_2025.03.11.642653v1.2","doi-asserted-by":"publisher","DOI":"10.1597\/10-178"},{"key":"2026041100154524000_2025.03.11.642653v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23076"},{"key":"2026041100154524000_2025.03.11.642653v1.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032909"},{"key":"2026041100154524000_2025.03.11.642653v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"2026041100154524000_2025.03.11.642653v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23596"},{"key":"2026041100154524000_2025.03.11.642653v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12823"},{"key":"2026041100154524000_2025.03.11.642653v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.580"},{"key":"2026041100154524000_2025.03.11.642653v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.08.021"},{"issue":"3","key":"2026041100154524000_2025.03.11.642653v1.10","first-page":"453","article-title":"The surface layer of human foetal skin and oral mucosa: a study by scanning and transmission electron microscopy","volume":"108","year":"1971","journal-title":"J Anat"},{"key":"2026041100154524000_2025.03.11.642653v1.11","doi-asserted-by":"publisher","DOI":"10.1242\/dev.067082"},{"key":"2026041100154524000_2025.03.11.642653v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2015.07.002"},{"key":"2026041100154524000_2025.03.11.642653v1.13","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_1995_032_0522_dotfap_2.3.co_2"},{"key":"2026041100154524000_2025.03.11.642653v1.14","doi-asserted-by":"publisher","DOI":"10.1242\/dev.103.Supplement.41"},{"key":"2026041100154524000_2025.03.11.642653v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.06.030"},{"key":"2026041100154524000_2025.03.11.642653v1.16","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.036442"},{"key":"2026041100154524000_2025.03.11.642653v1.17","doi-asserted-by":"publisher","DOI":"10.1086\/301956"},{"key":"2026041100154524000_2025.03.11.642653v1.18","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960513)368:4<620::AID-CNE12>3.0.CO;2-L"},{"key":"2026041100154524000_2025.03.11.642653v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.09.010"},{"key":"2026041100154524000_2025.03.11.642653v1.20","doi-asserted-by":"crossref","unstructured":"Lough, K.J. , et al., Disruption of the nectin-afadin complex recapitulates features of the human cleft lip\/palate syndrome CLPED1. 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