Nf2/FGFR1/AKT axis directs cranial neural crest-derived skull morphogenesis via collagen synthesis and trafficking.

ABSTRACT: Cranial neural crest cells (CNCs) play a critical role in craniofacial bone morphogenesis, engaging in intricate interactions with various molecular signals to ensure proper development, yet the molecular scaffolds coordinating these processes remain incompletely defined. Here, we identify neurofibromin 2 (Nf2) as a critical regulator to direct CNC-derived skull morphogenesis. Genetic ablation of Nf2 in murine CNCs causes severe craniofacial anomalies, featuring declined proliferation and increased apoptosis in osteoprogenitors, impaired type I collagen biosynthesis and trafficking, and aberrant osteogenic mineralization. Mechanistically, we uncover that Nf2 serves as a molecular linker that individually interacts with FGF receptor 1 (FGFR1) and Akt through spatially segregated phosphor-si

SUBMITTER: Huang Y 

PROVIDER: S-EPMC12487865 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature