Capdevila J, Johnson R L
Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center, University of Texas, Houston 77030, USA.
Dev Biol. 1998 May 15;197(2):205-17. doi: 10.1006/dbio.1997.8824.
The gene noggin, originally cloned in Xenopus, encodes a secreted factor expressed in the Spemann organizer, where it functions to oppose the ventralizing influence of bone morphogenetic proteins (BMPs). Noggin protein acts by binding directly to BMPs, thereby preventing them from interacting with their receptors. Here we describe the pattern of expression of the chicken noggin gene during somite and limb development, two tissues in which BMPs have been postulated to play essential patterning roles. We find that noggin is expressed in dynamic restricted patterns consistent with an important role in the modulation of BMP signaling. Using a replication competent retrovirus we have ectopically expressed noggin in developing somitic and limb bud mesoderm and observed phenotypes consistent with complete block of BMP activity. This includes suppression of lateral somite differentiation and, in the limb, complete inhibition of chondrogenesis and local suppression of programmed cell death. In addition, we find that ectopic noggin expression in the limb has no effect on anteroposterior limb pattern, suggesting that BMPs are unlikely to play a significant role in this process. Taken together,, our results indicate that noggin is a key regulator of vertebrate limb and somite patterning and suggest that the antagonistic Noggin-BMP interaction is a widely used mechanism to modulate BMP signaling during multiple inductive events in vertebrate embryogenesis.
头蛋白基因最初是在非洲爪蟾中克隆出来的，它编码一种在施佩曼组织者中表达的分泌因子，在那里它起到对抗骨形态发生蛋白（BMPs）腹侧化影响的作用。头蛋白通过直接与BMPs结合来发挥作用，从而阻止它们与受体相互作用。在此，我们描述了鸡头蛋白基因在体节和肢体发育过程中的表达模式，这两个组织中BMPs被认为发挥着重要的模式形成作用。我们发现头蛋白以动态受限的模式表达，这与它在调节BMP信号传导中起重要作用一致。利用一种具有复制能力的逆转录病毒，我们在发育中的体节和肢芽中胚层异位表达了头蛋白，并观察到与BMP活性完全阻断一致的表型。这包括抑制体节外侧分化，在肢体中则完全抑制软骨形成并局部抑制程序性细胞死亡。此外，我们发现肢体中异位表达头蛋白对肢体的前后模式没有影响，这表明BMPs在这个过程中不太可能发挥重要作用。综上所述，我们的结果表明头蛋白是脊椎动物肢体和体节模式形成的关键调节因子，并表明Noggin - BMP的拮抗相互作用是脊椎动物胚胎发育中多个诱导事件期间调节BMP信号传导的广泛使用的机制。
