{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:36:38Z","timestamp":1768505798726,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,16]]},"group-title":"Developmental Biology","reference-count":134,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of\n                  <jats:italic>Tfap2a<\/jats:italic>\n                  and\n                  <jats:italic>Tfap2b<\/jats:italic>\n                  in the murine neural crest even during the late migratory phase results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both\n                  <jats:italic>Tfap2<\/jats:italic>\n                  members dysregulated numerous midface GRN components involved in midface fusion, patterning, and differentiation. Notably,\n                  <jats:italic>Alx1\/3\/4<\/jats:italic>\n                  (\n                  <jats:italic>Alx<\/jats:italic>\n                  ) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates\n                  <jats:italic>Alx<\/jats:italic>\n                  gene expression.\n                  <jats:italic>TFAP2<\/jats:italic>\n                  and\n                  <jats:italic>ALX<\/jats:italic>\n                  co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion,\n                  <jats:italic>tfap2a<\/jats:italic>\n                  mutant zebrafish present abnormal\n                  <jats:italic>alx3<\/jats:italic>\n                  expression patterns, and the two genes display a genetic interaction in this species. Together, these data demonstrate a critical role for TFAP2 in regulating vertebrate midfacial development in part through ALX transcription factor gene expression.\n                <\/jats:p>","DOI":"10.1101\/2023.06.16.545376","type":"posted-content","created":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T03:10:10Z","timestamp":1686971410000},"source":"Crossref","is-referenced-by-count":0,"title":["TFAP2 paralogs regulate midfacial development in part through a conserved\n                  <i>ALX<\/i>\n                  genetic pathway"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-1286","authenticated-orcid":false,"given":"Timothy T","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4222-5235","authenticated-orcid":false,"given":"Jennyfer M","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela D","family":"Kiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth L","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2416-4603","authenticated-orcid":false,"given":"Trevor J","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-1704","authenticated-orcid":false,"given":"James T","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5958-5742","authenticated-orcid":false,"given":"Eric Van","family":"Otterloo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023062016001618000_2023.06.16.545376v1.1","doi-asserted-by":"crossref","unstructured":"Abe, M. , Cox, T. 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