DISRUPTION OF BMP SIGNALS IN EMBRYONIC XENOPUS ECTODERM LEADS TO DIRECT NEURAL INDUCTION
DISRUPTION OF BMP SIGNALS IN EMBRYONIC XENOPUS ECTODERM LEADS TO DIRECT NEURAL INDUCTION
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DOI：
10.1101/gad.9.23.2923
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发表时间：
1995-12-15
影响因子：
10.5
通讯作者：
CHO, KWY
中科院分区：
文献类型：
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作者：
HAWLEY, SHB;WUNNENBERGSTAPLETON, K;CHO, KWY
骨形态发生蛋白（BMPs）是转化生长因子- β (tgf - β)超家族的成员，与中胚层的模式有关。我们研究了爪蟾BMP-7 （XBMP-7）和BMP-4 （XBMP-4）以及激活素（另一种tgf - β相关分子）在早期发育中的作用，通过产生这些生长因子的显性阴性版本。突变是通过改变XBMP-7、XBMP-4和激活素活性二聚体成熟所需的切割位点而产生的。这些突变结构，被命名为Cm-XBMP-7， Cm-XBMP-4和cm -激活素，产生允许亚基二聚化的多肽，但不能成熟。Cm-XBMP-7和Cm-XBMP-4在爪蟾胚胎的腹缘区表达，而cm -激活素不表达，导致第二轴的发育，类似于截断的BMP受体的异位表达。这些结果表明，切割突变体在中胚层模式形成过程中干扰BMP信号。我们还发现Cm-XBMP-7或Cm-XBMP-4在动物帽外胚层的表达可直接诱导神经外胚层。Cm-XBMP-7和Cm-XBMP-4的神经诱导是特异性的，因为cm -激活素或vg - 1的异位表达不模仿相同的表型。Cm-XBMP-7和Cm-XBMP-4对神经模式的分子研究表明，只有前神经外胚层标记物在这些cm - xbmp的响应中表达。这些结果表明，爪蟾发育过程中BMP参与了外胚层的形成，神经诱导需要去除外胚层中的BMP信号。我们认为，神经诱导是通过一种默认机制发生的，因此，在发育中的爪蟾胚胎中，外胚层向神经外胚层的转化需要抑制BMP信号。
Bone morphogenetic proteins (BMPs), which have been implicated in the patterning of mesoderm, are members of the transforming growth factor-beta (TGF-beta) superfamily. We have investigated the roles of Xenopus BMP-7 (XBMP-7) and BMP-4 (XBMP-4), and activin (another TGF-beta-related molecule) in early development by generating dominant-negative versions of these growth factors. Mutations were generated by altering the cleavage sites that are required for maturation of the active dimeric forms of XBMP-7, XBMP-4, and activin. These mutant constructs, designated Cm-XBMP-7, Cm-XBMP-4, and Cm-activin, result in polypeptides that allow for dimerization of the subunits, but are incapable of maturation. Expression of Cm-XBMP-7 and Cm-XBMP-4, but not Cm-activin, in the ventral marginal zone of the Xenopus embryo results in the development of a secondary axis, similar to that seen by ectopic expression of the truncated BMP receptor. These results suggest that the cleavage mutants interfere with BMP signaling during mesodermal patterning. We also found that expression of Cm-XBMP-7 or Cm-XBMP-4 in animal cap ectoderm directly induces neuroectoderm The neural induction was specific for Cm-XBMP-7 and Cm-XBMP-4 because ectopic expression of Cm-activin or Vg-l did not mimic the same phenotype. Molecular study of neural patterning by Cm-XBMP-7 and Cm-XBMP-4 revealed that only anterior neuroectodermal markers are expressed in response to these Cm-XBMPs. These results suggest that the BMPs are involved in the specification of ectoderm in Xenopus development, and that neural induction requires the removal of BMP signals in the ectoderm. We propose that neural induction occurs by a default mechanism, whereby the inhibition of BMP signaling is required for the conversion of ectoderm to neuroectoderm in the developing Xenopus embryo.