Systems biology of the self-regulating morphogenetic gradient of the Xenopus gastrula.
Systems biology of the self-regulating morphogenetic gradient of the Xenopus gastrula.
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非洲爪蟾原肠胚自我调节形态发生梯度的系统生物学。
DOI：
10.1101/cshperspect.a001701
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发表时间：
2009
影响因子：
7.2
通讯作者：
DeRobertis,EM
中科院分区：
文献类型：
--
作者：
Plouhinec,Jean-Louis;DeRobertis,EM
形态发生场的概念是由实验胚胎学家提出的，用于解释胚胎的自我调节行为。这些领域一直是一个抽象的概念，直到最近利用遗传学、生物化学和理论建模的组合来确定它们的分子组成。研究最好的形态发生场模型之一是早期青蛙胚胎的背腹(D-V)模式。这种模式系统受骨形态发生蛋白(BMP)信号通路和错综复杂的分泌蛋白拮抗剂网络的调节。这种相互作用的蛋白质的生化途径在细胞外空间发挥作用，产生BMP信号的D-V梯度，在原肠形成期间细胞层的广泛形态发生运动中保持这种梯度。在BMPs的反向转录控制下，D-V区分为背侧中心和腹侧中心，分别位于低和高BMP信号区。图案的健壮性在两个不同的水平上得到保证。首先，在细胞外空间，分泌的BMP拮抗剂产生定向的BMP配体流向腹侧。这一流动是由Chordin抑制剂的受控蛋白分解和腹侧集中BMP信号的分子汇的存在驱动的。Tolloid金属蛋白酶和Chordin结合蛋白Crossveinless-2(CV2)是这个腹面下沉的关键成分。第二，通过细胞水平的转录反馈：背侧和腹侧信号中心通过转录反馈调节它们的BMP信号的大小和水平。这使得原肠胚一侧的细胞包含大约10,000个细胞，与胚胎相反极的细胞进行交流。
The morphogenetic field concept was proposed by experimental embryologists to account for the self-regulative behavior of embryos. Such fields have remained an abstract concept until the recent identification of their molecular components using a combination of genetics, biochemistry, and theoretical modeling. One of the best studied models of a morphogenetic field is the Dorsal-Ventral (D-V) patterning of the early frog embryo. This patterning system is regulated by the bone morphogenetic protein (BMP) signaling pathway and an intricate network of secreted protein antagonists. This biochemical pathway of interacting proteins functions in the extracellular space to generate a D-V gradient of BMP signaling, which is maintained during extensive morphogenetic movements of cell layers during gastrulation. The D-V field is divided into a dorsal and a ventral center, in regions of low and high BMP signaling respectively, under opposite transcriptional control by BMPs. The robustness of the patterning is assured at two different levels. First, in the extracellular space by secreted BMP antagonists that generate a directional flow of BMP ligands to the ventral side. The flow is driven by the regulated proteolysis of the Chordin inhibitor and by the presence of a molecular sink on the ventral side that concentrates BMP signals. The tolloid metalloproteinases and the Chordin-binding protein Crossveinless-2 (CV2) are key components of this ventral sink. Second, by transcriptional feedback at the cellular level: The dorsal and ventral signaling centers adjust their size and level of BMP signaling by transcriptional feedback. This allows cells on one side of a gastrula containing about 10,000 cells to communicate with cells in the opposite pole of the embryo.