{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T04:41:45Z","timestamp":1775968905016,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,6]]},"group-title":"Developmental Biology","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["R01DE027091"],"award-info":[{"award-number":["R01DE027091"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Human congenital anomalies account for twice the mortality of childhood cancer. Despite advancements in genome sequencing and transgenic mouse models that have aided in understanding their pathogenesis, significant gaps remain. Through a forward genetics approach, we previously discovered the hypo-morphic\n                  <jats:italic>anteater<\/jats:italic>\n                  allele of\n                  <jats:italic>Cse1l<\/jats:italic>\n                  which displayed variable craniofacial phenotypes. To circumvent the variability seen in this model, we generated a conditional allele of\n                  <jats:italic>Cse1l<\/jats:italic>\n                  and genetically ablated it in the dorsal midline giving rise to portions of the nervous system and the cranial neural crest cells using the\n                  <jats:italic>Wnt1-Cre<\/jats:italic>\n                  2 driver. Our analysis revealed that\n                  <jats:italic>Wnt1-Cre2; Cse1l<\/jats:italic>\n                  <jats:sup>\n                    <jats:italic>CRISPR\/flox<\/jats:italic>\n                  <\/jats:sup>\n                  embryos exhibited severe malformations in the forebrain, midbrain, and hindbrain, accompanied by a dramatic hypoplasia of the frontonasal, maxillary, and mandibular processes, and the second pharyngeal arch.\n                  <jats:italic>Wnt1-Cre2; Cse1l<\/jats:italic>\n                  <jats:sup>\n                    <jats:italic>CRISPR\/flox<\/jats:italic>\n                  <\/jats:sup>\n                  embryos were embryonic lethal by E11.5 likely due to defects in the ventricular myocardium.\n                  <jats:italic>Wnt1-Cre2; Cse1l<\/jats:italic>\n                  <jats:sup>\n                    <jats:italic>CRISPR\/flox<\/jats:italic>\n                  <\/jats:sup>\n                  embryos exhibited consistently increased apoptosis at E9.5 in the affected tissues along with an increase in p53 expression. These data together show a previously unknown critical function of CSE1L in neural crest cell survival during development.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary Statement<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Cse1l<\/jats:italic>\n                    is critical for neural crest cell survival and genetic ablation of\n                    <jats:italic>Cse1l<\/jats:italic>\n                    in neural crest cells resulted in dramatic apoptosis with increase in p53 expression.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.06.652282","type":"posted-content","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T16:15:12Z","timestamp":1746548112000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Cse1l<\/i>\n                  Regulates Neural Crest Cell Survival and is Critical for Craniofacial and Cardiac Development"],"prefix":"10.64898","author":[{"given":"Paul P. R.","family":"Iyyanar","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"}]},{"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, 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