biostudies-literatureIonescu ANIDDK NIH HHSNIAMS NIH HHS927-39https://www.ebi.ac.uk/biostudies/studies/S-EPMC3356573biostudies-literatureUnknown22(5)During endochondral ossification, small, immature chondrocytes enlarge to form hypertrophic chondrocytes, which express collagen X. In this work, we demonstrate that FoxA factors are induced during chondrogenesis, bind to conserved binding sites in the collagen X enhancer, and can promote the expression of a collagen X-luciferase reporter in both chondrocytes and fibroblasts. In addition, we demonstrate by both gain- and loss-of-function analyses that FoxA factors play a crucial role in driving the expression of both endogenous collagen X and other hypertrophic chondrocyte-specific genes. Mice engineered to lack expression of both FoxA2 and FoxA3 in their chondrocytes display defects in chondrocyte hypertrophy, alkaline phosphatase expression, and mineralization in their sternebrae and, inDevelopmental cellFoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program.PMC3356573R01 AR036820DK049210R01 AR055552-02R01 AR048524-09AR055552AR36819DK054342AR36820R01 AR036819R37 AR036819R01 AR048524P01 DK049210R01 AR055552R01 AR055552-03AR048524Lassar ABKaestner KHIonescu ANicolae CKozhemyakina EOlsen BRfalseFoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program.During endochondral ossification, small, immature chondrocytes enlarge to form hypertrophic chondrocytes, which express collagen X. In this work, we demonstrate that FoxA factors are induced during chondrogenesis, bind to conserved binding sites in the collagen X enhancer, and can promote the expression of a collagen X-luciferase reporter in both chondrocytes and fibroblasts. In addition, we demonstrate by both gain- and loss-of-function analyses that FoxA factors play a crucial role in driving the expression of both endogenous collagen X and other hypertrophic chondrocyte-specific genes. Mice engineered to lack expression of both FoxA2 and FoxA3 in their chondrocytes display defects in chondrocyte hypertrophy, alkaline phosphatase expression, and mineralization in their sternebrae and, in2012-01-01T00:00:00Z2012 May2025-04-21T16:31:03.443Z2019-03-27T00:53:39ZS-EPMC33565732259566810.1016/j.devcel.2012.03.011