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Separating these bones are fibrous sutures that permit growth. Currently, we do not understand the instructions for directional growth of the calvaria, a process which is error-prone and can lead to skeletal deficiencies or premature suture fusion (craniosynostosis, CS). Here, we identify graded expression of fibronectin (FN1) in the mouse embryonic cranial mesenchyme (CM) that precedes the apical expansion of calvaria. Conditional deletion of Fn1 or Wasl leads to diminished frontal bone expansion by altering cell shape and focal actin enrichment, respectively, suggesting defective migration of calvarial progenitors. Interestingly, Fn1 mutants have premature fusion of coronal sutures. Consistently, syndromic forms of CS in humans exhibit dysregulated FN1 expression, and we also find FN1 expression altered in a mouse CS model of Apert syndrome. These data support a model of FN1 as a directional substrate for calvarial osteoblast migration that may be a common mechanism underlying many cranial disorders of disparate genetic etiologies.<\/jats:p>","DOI":"10.1242\/dev.202371","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T09:59:19Z","timestamp":1712829559000},"source":"Crossref","is-referenced-by-count":6,"title":["Apical expansion of calvarial osteoblasts and suture patency is dependent on fibronectin cues"],"prefix":"10.1242","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-5536","authenticated-orcid":false,"given":"Xiaotian","family":"Feng","sequence":"first","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-3288","authenticated-orcid":false,"given":"Helen","family":"Molteni","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1197-5949","authenticated-orcid":false,"given":"Megan","family":"Gregory","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3640-6996","authenticated-orcid":false,"given":"Jennifer","family":"Lanza","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5343-4759","authenticated-orcid":false,"given":"Nikaya","family":"Polsani","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5198-9907","authenticated-orcid":false,"given":"Isha","family":"Gupta","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-7044","authenticated-orcid":false,"given":"Rachel","family":"Wyetzner","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5164-2893","authenticated-orcid":false,"given":"M. Brent","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Harvard Medical School 2 Department of Genetics , , Department of Orthopedics , , Boston, MA 02115 , USA"},{"name":"Boston Children's Hospital 2 Department of Genetics , , Department of Orthopedics , , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-6722","authenticated-orcid":false,"given":"Greg","family":"Holmes","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai 3 Department of Genetics and Genomic Sciences , , New York, NY 10029 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-8902","authenticated-orcid":false,"given":"Sevan","family":"Hopyan","sequence":"additional","affiliation":[{"name":"Hospital for Sick Kids 4 Department of Developmental Biology , , Toronto ON, M5G 0A4 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7201-4693","authenticated-orcid":false,"given":"Matthew P.","family":"Harris","sequence":"additional","affiliation":[{"name":"Harvard Medical School 2 Department of Genetics , , Department of Orthopedics , , Boston, MA 02115 , USA"},{"name":"Boston Children's Hospital 2 Department of Genetics , , Department of Orthopedics , , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-6552","authenticated-orcid":false,"given":"Radhika P.","family":"Atit","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Biology , , Cleveland, OH 44106 , USA"},{"name":"Case Western Reserve University, Cleveland, OH 44106 5 Department of Genome Sciences and Genetics , , USA"},{"name":"Case Western Reserve University, Cleveland, OH 44106 6 Department of Dermatology , , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"2024041113591396200_DEV202371C1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bbrc.2019.02.106","article-title":"Cdc42 regulates cranial suture morphogenesis and ossification","volume":"512","author":"Aizawa","year":"2019","journal-title":"Biochem. 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