鸡转录抑制因子Nkx3.2在音猬因子（Shh）下游发挥作用，以促进骨形态发生蛋白（BMP）依赖的轴向软骨形成。

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

作者信息

Murtaugh L C, Zeng L, Chyung J H, Lassar A B

机构信息

Department of Biological Chemistry and Molecular Pharmacy, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Dev Cell. 2001 Sep;1(3):411-22. doi: 10.1016/s1534-5807(01)00039-9.

DOI:10.1016/s1534-5807(01)00039-9

PMID:11702952

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.

摘要

此前，我们证明了 Sonic Hedgehog（Shh）在轴向骨骼发育早期发挥作用，诱导对后期骨形态发生蛋白（BMP）信号的软骨生成前期反应。在此，我们证明转录因子 Nkx3.2 在体节中的表达由 Shh 启动，并由 BMP 信号维持。Nkx3.2 在体节组织中的错误表达赋予了对 BMP 信号的软骨生成前期反应。Nkx3.2 的转录抑制活性对于该因子促进软骨形成至关重要。相反，已转化为转录激活剂的 Nkx3.2 的“反向功能”突变体在体内抑制轴向软骨生成。我们得出结论，Nkx3.2 是 Shh 在轴向软骨形成过程中作用的关键介质，其作用是抑制干扰 BMP 软骨生成前期作用的因子的表达。