Fibronectin 1 is required for suture patency and dysregulated across craniosynostosis models in the mouse

Area of Science:

• Developmental Biology
• Genetics
• Biochemistry

Background:

• The mammalian skull roof protects the brain and facilitates growth via fibrous sutures.
• Craniosynostosis (CS), premature suture closure affecting 1 in 2500 newborns, results from genetic heterogeneity but shares a common phenotype.
• Fibronectin (FN1), an extracellular matrix protein, is crucial for calvarial expansion and coronal suture patency.

Purpose of the Study:

• To investigate the cellular mechanisms underlying CS in Fibronectin-deficient (Fn1) mutant mice.
• To explore the role of FN1 dysregulation as a convergent etiological mechanism in syndromic and non-syndromic CS.
• To identify FN1 as a potential therapeutic target for matrix-mediated CS treatments.

Main Methods:

• Analysis of Fn1 mutant mouse models exhibiting craniosynostosis.
• Assessment of baso-apical FN1 expression patterns in cranial mesenchyme.
• Evaluation of frontal bone primordia expansion and suture mesenchyme cell identity and differentiation.

Main Results:

• Variably dysregulated baso-apical FN1 expression was observed in CS mouse models.
• Diminished apical expansion of frontal bone primordia correlated with FN1 dysregulation.
• Ectopic osteogenic induction of Six2+ patent suture mesenchyme occurred in Fn1 mutants at later stages.

Conclusions:

• Fibronectin (FN1) is a critical regulator of skull suture patency.
• FN1 modulates calvarial growth and influences cell identity and differentiation, impacting suture development.
• Targeting FN1 offers a potential strategy for matrix-mediated treatments for craniosynostosis.