Kida Yasuyuki, Maeda Yukiko, Shiraishi Tomoki, Suzuki Takayuki, Ogura Toshihiko
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara, 630-0101, Japan.
Development. 2004 Sep;131(17):4179-87. doi: 10.1242/dev.01252. Epub 2004 Jul 27.
Based on recent data, a new view is emerging that vertebrate Dachshund (Dach) proteins are components of Six1/6 transcription factor-dependent signaling cascades. Although Drosophila data strongly suggest a tight link between Dpp signaling and the Dachshund gene, a functional relationship between vertebrate Dach and BMP signaling remains undemonstrated. We report that chick Dach1 interacts with the Smad complex and the corepressor mouse Sin3a, thereby acting as a repressor of BMP-mediated transcriptional control. In the limb, this antagonistic action regulates the formation of the apical ectodermal ridge (AER) in both the mesenchyme and the AER itself, and also controls pattern formation along the proximodistal axis of the limb. Our data introduce a new paradigm of BMP antagonism during limb development mediated by Dach1, which is now proven to function in different signaling cascades with distinct interacting partners.
基于最近的数据，一种新的观点正在形成，即脊椎动物的腊肠犬（Dach）蛋白是Six1/6转录因子依赖性信号级联反应的组成部分。尽管果蝇的数据有力地表明了Dpp信号与腊肠犬基因之间存在紧密联系，但脊椎动物Dach与BMP信号之间的功能关系仍未得到证实。我们报告称，鸡Dach1与Smad复合体和共抑制因子小鼠Sin3a相互作用，从而作为BMP介导的转录控制的抑制因子发挥作用。在肢体中，这种拮抗作用调节间充质和顶端外胚层嵴（AER）本身中AER的形成，并且还控制沿着肢体近远轴的模式形成。我们的数据引入了一种由Dach1介导的肢体发育过程中BMP拮抗作用的新范式，现在已证明Dach1在与不同相互作用伙伴的不同信号级联反应中发挥作用。
