The chick transcriptional repressor Nkx3.2 acts downstream of Shh to promote BMP-dependent axial chondrogenesis

Abstract

Previously, we demonstrated that Shh acts early in the development of the axial skeleton, to induce a prochondrogenic response to later BMP signaling. Here, we demonstrate that somitic expression of the transcription factor Nkx3.2 is initiated by Shh and sustained by BMP signals. Misexpression of Nkx3.2 in somitic tissue confers a prochondrogenic response to BMP signals. The transcriptional repressor activity of Nkx3.2 is essential for this factor to promote chondrogenesis. Conversely, a "reverse function" mutant of Nkx3.2 that has been converted into a transcriptional activator inhibits axial chondrogenesis in vivo. We conclude that Nkx3.2 is a critical mediator of the actions of Shh during axial cartilage formation, acting to inhibit expression of factors that interfere with the prochondrogenic effects of BMPs.