{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:24:33Z","timestamp":1768505073526,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,16]]},"group-title":"Developmental Biology","reference-count":77,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,16]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The skull roof, or calvaria, is comprised of interlocking plates of bone. Premature suture fusion (craniosynostosis, CS) or persistent fontanelles are common defects in calvarial development. Although some of the genetic causes of these disorders are known, we lack an understanding of the instructions directing the growth and migration of progenitors of these bones, which may affect the suture patency. Here, we identify graded expression of Fibronectin (FN1) protein in the mouse embryonic cranial mesenchyme (CM) that precedes the apical expansion of calvarial osteoblasts. Syndromic forms of CS exhibit dysregulated FN1 expression, and we find FN1 expression is altered in a mouse CS model as well. Conditional deletion of\n                  <jats:italic>Fn1<\/jats:italic>\n                  in CM causes diminished frontal bone expansion by altering cell polarity and shape. To address how osteoprogenitors interact with the observed FN1 prepattern, we conditionally ablate\n                  <jats:italic>Wasl\/N-Wasp<\/jats:italic>\n                  to disrupt F-actin junctions in migrating cells, impacting lamellipodia and cell-matrix interaction. Neural crest-targeted deletion of\n                  <jats:italic>Wasl<\/jats:italic>\n                  results in a diminished actin network and reduced expansion of frontal bone primordia similar to conditional\n                  <jats:italic>Fn1<\/jats:italic>\n                  mutants. Interestingly, defective calvaria formation in both the\n                  <jats:italic>Fn1<\/jats:italic>\n                  and\n                  <jats:italic>Wasl<\/jats:italic>\n                  mutants occurs without a significant change in proliferation, survival, or osteogenesis. Finally, we find that CM-restricted\n                  <jats:italic>Fn1<\/jats:italic>\n                  deletion leads to premature fusion of coronal sutures. 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.\n                <\/jats:p>","DOI":"10.1101\/2023.01.16.524278","type":"posted-content","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T06:15:36Z","timestamp":1673936136000},"source":"Crossref","is-referenced-by-count":1,"title":["Apical expansion of calvarial osteoblasts and suture patency is dependent on graded fibronectin cues"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8736-5536","authenticated-orcid":false,"given":"Xiaotian","family":"Feng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-3288","authenticated-orcid":false,"given":"Helen","family":"Molteni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1197-5949","authenticated-orcid":false,"given":"Megan","family":"Gregory","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3640-6996","authenticated-orcid":false,"given":"Jennifer","family":"Lanza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5343-4759","authenticated-orcid":false,"given":"Nikaya","family":"Polsani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-7044","authenticated-orcid":false,"given":"Rachel","family":"Wyetzner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5164-2893","authenticated-orcid":false,"given":"M. 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