Takahashi M, Tamura K, Büscher D, Masuya H, Yonei-Tamura S, Matsumoto K, Naitoh-Matsuo M, Takeuchi J, Ogura K, Shiroishi T, Ogura T, Izpisúa Belmonte J C
The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, CA 92037-1099, USA.
Development. 1998 Nov;125(22):4417-25. doi: 10.1242/dev.125.22.4417.
We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.
我们已经确定，斯特朗氏鲁克索德（lstJ）[已修正]小鼠的Alx-4基因同源框区域存在16个碱基对的缺失。这种缺失导致阅读框移位和Alx-4蛋白截短，可能是lstJ[已修正]小鼠中观察到的多指表型的原因。我们克隆了Alx-4的鸡同源物，并研究了其在肢体生长过程中的表达情况。鸡Alx-4的表达模式与shh互补，shh是肢芽中极化活性的介导因子。除了外胚层顶嵴去除实验外，局部应用音猬因子（Shh）和成纤维细胞生长因子（FGF）表明，在肢体生长过程中，Alx-4和Shh之间存在负反馈回路。对多指突变体的分析表明，Alx-4和Shh之间的相互作用独立于Gli3，Gli3是肢体中Shh的负调节因子。我们的数据表明，在脊椎动物肢体生长过程中，Alx-4和Shh之间存在负反馈回路。
