Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1.
Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1.
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发表时间：
1997-08
期刊：
影响因子：
4.6
通讯作者：
Paul A. Wilson;Giorgio Lagna;Atsushi Suzuki;A. Hemmati‐Brivanlou
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作者：
Paul A. Wilson;Giorgio Lagna;Atsushi Suzuki;A. Hemmati‐Brivanlou
形态发生素被认为是在早期胚胎中建立模式，通过指定几个细胞的命运沿着浓度梯度;一个研究得很好的例子是果蝇蛋白decapentaplegic（DPP）在翅盘中起作用。最近的工作已经确定，骨形态发生蛋白4（BMP 4），脊椎动物的同源物的DPP，控制的基本选择之间的神经和表皮的命运在脊椎动物外胚层，由中胚层的组织者区域分泌的拮抗剂的控制下。我们现在表明，BMP 4可以作为一种形态发生剂，在高浓度和低浓度下引起爪蟾外胚层细胞的不同反应，其模式与胚胎中相应细胞类型的位置一致。此外，这种对细胞外BMP 4浓度的复杂细胞应答不需要随后的细胞-细胞通信，因此是直接的，如经典形态发生素所要求的。我们还表明，同一系列的细胞类型-表皮，水泥腺和神经组织-可以通过逐步抑制内源性BMP信号与特定的拮抗剂，包括组织因子头蛋白。最后，增加剂量的信号转导分子Smad 1的表达准确地再现了对BMP 4蛋白的反应。由于Smads已被证明在细胞核中起作用，这一发现意味着细胞外形态原浓度直接转化为转录因子活性。我们建议，BMP活性的分级分布控制几种细胞类型的规范在原肠胚外胚层，这种细胞外梯度的行为，通过建立一个细胞内，然后核梯度的Smad活性。
Morphogens are thought to establish pattern in early embryos by specifying several cell fates along a gradient of concentration; a well-studied example is the Drosophila protein decapentaplegic (DPP) acting in the wing disc. Recent work has established that bone morphogenetic protein 4 (BMP4), the vertebrate homologue of DPP, controls the fundamental choice between neural and epidermal fates in the vertebrate ectoderm, under the control of antagonists secreted by the organizer region of the mesoderm. We now show that BMP4 can act as a morphogen, evoking distinct responses in Xenopus ectodermal cells at high and low concentrations, in a pattern consistent with the positions of the corresponding cell types in the embryo. Moreover, this complex cellular response to extracellular BMP4 concentration does not require subsequent cell-cell communication and is thus direct, as required of a classical morphogen. We also show that the same series of cell types--epidermis, cement gland and neural tissue--can be produced by progressively inhibiting endogenous BMP signaling with specific antagonists, including the organizer factor noggin. Finally, expression of increasing doses of the signal transduction molecule Smad1 accurately reproduces the response to BMP4 protein. Since Smads have been shown to act in the nucleus, this finding implies a direct translation of extracellular morphogen concentration into transcription factor activity. We propose that a graded distribution of BMP activity controls the specification of several cell types in the gastrula ectoderm and that this extracellular gradient acts by establishing an intracellular and then nuclear gradient of Smad activity.