Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite
Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite
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DOI：
10.1101/gad.12.10.1438
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发表时间：
1998-05-15
影响因子：
10.5
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
McMahon, JA;Takada, S;McMahon, AP
脊椎动物的胚胎模式化依赖于诱导信号及其特异性拮抗剂的平衡。我们发现，Noggin，它编码的骨形态发生蛋白（BMP）拮抗剂的节点，脊索，背体节中表达，是正常小鼠发育所需的。虽然Noggin与神经诱导有关，但对小鼠中的无效突变体的检查表明Noggin对于该过程不是必需的。然而，Noggin是神经管随后生长和形成图案所必需的。早期BMP依赖的背细胞命运，顶板和神经嵴，在没有Noggin的情况下形成。然而，尽管Shh在脊索中表达正常，但早期的Sonic hedgehog（Shh）依赖的腹侧细胞命运逐渐丧失。此外，体节分化是缺乏肌肉和sclerotomal前体。向近轴中胚层外植体中添加BMP 2或BMP 4阻断Shh介导的Pax-1（一种菌核标记物）诱导，而添加头蛋白足以诱导Pax-1。Noggin和Shh协同诱导Pax-1。使用蛋白激酶A刺激剂阻断Shh介导的Pax-1诱导，但不阻断Noggin诱导，表明诱导是由不同途径介导的。总之，这些数据表明，轴向分泌的头蛋白对BMP信号传导的抑制是脊椎动物神经管和体节正常模式化的重要要求。
Embryonic patterning in vertebrates is dependent upon the balance of inductive signals and their specific antagonists. We show that Noggin, which encodes a bone morphogenetic protein (BMP) antagonist expressed in the node, notochord, and dorsal somite, is required for normal mouse development. Although Noggin has been implicated in neural induction, examination of null mutants in the mouse indicates that Noggin is not essential for this process. However, Noggin is required for subsequent growth and patterning of the neural tube. Early BMP-dependent dorsal cell fates, the roof plate and neural crest, form in the absence of Noggin. However, there is a progressive loss of early, Sonic hedgehog (Shh)-dependent ventral cell fates despite the normal expression of Shh in the notochord. Further, somite differentiation is deficient in both muscle and sclerotomal precursors. Addition of BMP2 or BMP4 to paraxial mesoderm explants blocks Shh-mediated induction of Pax-1, a sclerotomal marker, whereas addition of Noggin is sufficient to induce Pax-1. Noggin and Shh induce Pax-1 synergistically. Use of protein kinase A stimulators blocks Shh-mediated induction of Pax-1, but not induction by Noggin, suggesting that induction is mediated by different pathways. Together these data demonstrate that inhibition of BMP signaling by axially secreted Noggin is an important requirement for normal patterning of the vertebrate neural tube and somite.