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FGFR2 Directs Inhibition of WNT Signaling to Regulate Anterior Fontanelle Closure during Skull Development

ABSTRACT: The calvarial bones of the infant skull are linked by transient fibrous joints known as sutures and fontanelles, which are essential for skull compression during birth and expansion during postnatal brain growth. Genetic conditions caused by pathogenic variants in FGFR2, such as Apert, Pfeiffer, Crouzon syndromes, result in calvarial deformities due to premature suture fusion and a persistently open anterior fontanelle (AF). In this study we investigated how Fgfr2 regulates AF closure by leveraging mouse genetics and single-cell transcriptomics. We find that AF cells, marked by the tendon/ligament factor SCX, are spatially organized into ecto- and endocranial domains that selectively differentiate into ligament, bone, and cartilage to form the posterior frontal suture. We show that AF cell differentiation is non-autonomously regulated by FGFR2 signaling in osteogenic front cells of the frontal bones, which regulate WNT signaling in neighboring AF cells by expressing the secreted WNT inhibitor Wif1. Upon loss of Fgfr2, Wif1 expression is downregulated, and AF cells fail to form the posterior frontal suture. This study identifies an FGF-WNT signaling circuit that that directs suture formation within the AF during postnatal development.

ORGANISM(S): Mus musculus

PROVIDER: GSE286314 | GEO | 2025/01/14

REPOSITORIES: GEO

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