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BOR is characterized by craniofacial defects, including malformed middle ear ossicles leading to conductive hearing loss. In this work, we expand our knowledge of the <jats:italic>Six1<\/jats:italic> gene regulatory network by using a <jats:italic>Six1\u2010null<\/jats:italic> mouse line to assess gene expression profiles of E10.5 mandibular arches, which give rise to the neural crest (NC)\u2010derived middle ear ossicles and lower jaw, via bulk RNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our transcriptomic analysis led to the identification of 808 differentially expressed genes that are related to translation, NC cell differentiation, osteogenesis, and chondrogenesis including components of the WNT signaling pathway. As WNT signaling is a known contributor to bone development, we demonstrated that SIX1 is required for expression of the WNT antagonist <jats:italic>Frzb<\/jats:italic> in the mandibular arch, and determined that SIX1 expression results in repression of WNT signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results clarify the mechanisms by which SIX1 regulates the development of NC\u2010derived craniofacial elements that are altered in SIX1\u2010associated disorders. In addition, this work identifies novel genes that could be causative to this birth defect and establishes a link between SIX1 and WNT signaling during patterning of NC cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.597","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T05:45:40Z","timestamp":1684129540000},"page":"1303-1315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Transcriptomic analysis reveals the role of <scp>SIX1<\/scp> in mouse cranial neural crest patterning and bone development"],"prefix":"10.1002","volume":"252","author":[{"given":"Aparna","family":"Baxi","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn","family":"Jourdeuil","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.","family":"Cox","sequence":"additional","affiliation":[{"name":"Departments of Oral and Craniofacial Sciences and Pediatrics University of Missouri\u2010Kansas City  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Clouthier","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9893-2305","authenticated-orcid":false,"given":"Andre L. 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