Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb
Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb
复制标题
DOI：
10.1016/j.ydbio.2009.04.038
复制
发表时间：
2009-07-15
影响因子：
2.7
通讯作者：
Robert, Benoit
中科院分区：
文献类型：
--
作者：
Lallemand, Yvan;Bensoussan, Vardina;Robert, Benoit
在四足动物中，肢体的前后 (AP) 模式受到分泌因子 Sonic hidehog (Shh) 和 Gli3R（转录因子 GO 的截短阻遏形式）的拮抗活动的控制。在本报告中，我们表明 Msx1 和 Msx2 是 Gli3R 的靶标和下游效应子。因此，在 Shh 无效突变体中，Msx 基因过度表达，而且对肢体表型有部分影响。降低 Shh 突变体中的 Msx 活性可以部分恢复正常的肢体发育，这一事实证明了这一点。最后，我们表明Msx基因在正常和Shh(-/-)肢体发育中的主要作用是控制间充质中的细胞死亡。我们提出，在肢体中，Msx 基因通过转导 BMP 信号传导在 Shh/Gli3 通路下游发挥作用，并且在缺乏 Shh 信号传导的情况下，它们的失调会导致广泛的细胞凋亡，从而损害肢体发育。 (C) 2009 Elsevier Inc. 保留所有权利。
In tetrapods, the anteroposterior (AP) patterning of the limb is under the control of the antagonistic activities of the secreted factor Sonic hedgehog (Shh) and Gli3R, the truncated repressor form of the transcription factor GO. In this report, we show that Msx1 and Msx2 are targets and downstream effectors of Gli3R. Consequently, in Shh null Mutants, Msx genes are overexpressed and, furthermore, partially responsible for the limb phenotype. This is exemplified by the fact that reducing Msx activity in Shh mutants partially restores a normal limb development. Finally, we show that the main action of the Msx genes, in both normal and Shh(-/-) limb development, is to control cell death in the mesenchyme. We propose that, in the limb, Msx genes act downstream of the Shh/Gli3 pathway by transducing BMP signaling and that, in the absence of Shh signaling, their deregulation contributes to the extensive apoptosis that impairs limb development. (C) 2009 Elsevier Inc. All rights reserved.