{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:39:52Z","timestamp":1768509592280,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,2]]},"group-title":"Developmental Biology","reference-count":47,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Nager syndrome is a rare craniofacial and limb disorder characterized by midface retrusion, micrognathia, absent thumbs, and radial hypoplasia. This disorder results from haploinsufficiency of SF3B4 (splicing factor 3b, subunit 4) a component of the pre-mRNA spliceosomal machinery. The spliceosome is a complex of RNA and proteins that function together to remove introns and join exons from transcribed pre-mRNA. While the spliceosome is present and functions in all cells of the body, most spliceosomopathies \u2013 including Nager syndrome \u2013 are cell\/tissue-specific in their pathology. In Nager syndrome patients, it is the neural crest (NC)-derived craniofacial skeletal structures that are primarily affected. To understand the pathomechanism underlying this condition, we generated a\n                  <jats:italic>Xenopus tropicalis sf3b4<\/jats:italic>\n                  mutant line using the CRISPR\/Cas9 gene editing technology. Here we describe the\n                  <jats:italic>sf3b4<\/jats:italic>\n                  mutant phenotype at neurula, tail bud, and tadpole stages, and performed temporal RNA-sequencing analysis to characterize the splicing events and transcriptional changes underlying this phenotype. Our data show that while loss of one copy of\n                  <jats:italic>sf3b4<\/jats:italic>\n                  is largely inconsequential in\n                  <jats:italic>Xenopus tropicalis<\/jats:italic>\n                  , homozygous deletion of\n                  <jats:italic>sf3b4<\/jats:italic>\n                  causes major splicing defects and massive gene dysregulation, which disrupt cranial NC cell migration and survival, thereby pointing at an essential role of Sf3b4 in craniofacial development.\n                <\/jats:p>","DOI":"10.1101\/2024.01.31.578190","type":"posted-content","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T18:55:27Z","timestamp":1706900127000},"source":"Crossref","is-referenced-by-count":4,"title":["<i>Sf3b4<\/i>\n                  mutation in\n                  <i>Xenopus tropicalis<\/i>\n                  causes RNA splicing defects followed by massive gene dysregulation that disrupt cranial neural crest development"],"prefix":"10.64898","author":[{"given":"Casey","family":"Griffin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey","family":"Coppenrath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doha","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marko","family":"Horb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"Saint-Jeannet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024020512000769000_2024.01.31.578190v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.3.355"},{"key":"2024020512000769000_2024.01.31.578190v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00161-1"},{"key":"2024020512000769000_2024.01.31.578190v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.04.004"},{"key":"2024020512000769000_2024.01.31.578190v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab051"},{"key":"2024020512000769000_2024.01.31.578190v1.5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/dvdy.183","article-title":"Spliceosomopathiesand neurocristopathies: two sides of the same coin?","volume":"249","year":"2020","journal-title":"Developmental Dynamics"},{"key":"2024020512000769000_2024.01.31.578190v1.6","doi-asserted-by":"crossref","unstructured":"Bolger, A.M. , Lohse, M. , Usadel, B . 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