Apical expansion of calvarial osteoblasts and suture patency is dependent on fibronectin cues

Xiaotian Feng, Helen Molteni, Megan Gregory, Jennifer Lanza, Nikaya Polsani, Isha Gupta, Rachel Wyetzner, M. Brent Hawkins, Greg Holmes, Sevan Hopyan, Matthew P. Harris, Radhika P. Atit

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The skull roof, or calvaria, is comprised of interlocking plates of bones that encase the brain. 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.

Original languageEnglish
Article numberdev202371
JournalDevelopment (Cambridge)
Volume151
Issue number7
DOIs
StatePublished - Mar 2024

Keywords

  • Apical expansion
  • Craniosynostosis
  • Mouse calvaria
  • Wasl/N-Wasp

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