Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.

ABSTRACT: Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue separation. Apoptosis has been detected in phalangeal joints during development, but its role and regulation have not been defined. Here, we use a mouse model of brachydactyly type A1 (BDA1) with an Ihh^E95K mutation, to show that a missing middle phalangeal bone is due to the failure of the developing joint to cavitate, associated with reduced apoptosis, and a joint is not formed. We showed an intricate relationship between IHH and interacting partners, CDON and GAS1, in the interzone that regulates apoptosis. We propose a model in

SUBMITTER: Leung AOW 

PROVIDER: S-EPMC10933404 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature