Disruption of a hedgehog-foxf1-rspo2 signaling axis leads to tracheomalacia and a loss of sox9+ tracheal chondrocytes.

ABSTRACT: Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multiple HH/Gli mouse mutants including one that mimics Pallister-Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH/Gli signaling results in 1) loss of Foxf1 which in turn is

SUBMITTER: Nasr T 

PROVIDER: S-EPMC7875488 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature