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Defining the critical period of hedgehog pathway inhibitor‐induced cranial base dysplasia in mice
Author(s) -
Chen Jiangping,
Tang Wenbing,
Lin Chengquan,
Hong Yuhang,
Mao Chuanqing,
Lai Yongzhen,
Liao Caiyu,
Lin Minkui,
Chen Weihui
Publication year - 2021
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.270
Subject(s) - vismodegib , craniosynostosis , biology , craniofacial , skull , hedgehog signaling pathway , anatomy , hedgehog , sonic hedgehog , microbiology and biotechnology , signal transduction , genetics
Background The hedgehog signaling pathway is critical for developmental patterning of the limb, craniofacial and axial skeleton. Disruption of this pathway in mice leads to a series of structural malformations, but the exact role and critical period of the Hh pathway in the early development of the cranial base have been rarely described. Results Embryos exposed to vismodegib from E7.5, E9.5, and E10.5 had a higher percentage of cranial base fenestra. The peak incidence of hypoplasia in sphenoid winglets and severe craniosynostosis in cranial base synchondroses was observed when vismodegib was administered between E9.5 and E10.5. Cranial base craniosynostosis results from accelerating terminal differentiation of chondrocytes and premature osteogenesis. Conclusions We define the critical periods for the induction of cranial base deformity by vismodegib administration at a meticulous temporal resolution. Our findings suggest that the Hh pathway may play a vital role in the early development of the cranial base. This research also establishes a novel and easy‐to‐establish mouse model of synostosis in the cranial base using a commercially available pathway‐selective inhibitor.