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爪蟾原肠胚自我调节形态发生梯度的系统生物学。

Systems biology of the self-regulating morphogenetic gradient of the Xenopus gastrula.

机构信息

Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, California 90095-1662, USA.

出版信息

Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a001701. doi: 10.1101/cshperspect.a001701.

Abstract

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.

摘要

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。直到最近,通过遗传学、生物化学和理论建模的结合,才确定了这些场的分子成分,在此之前,它们一直是一个抽象的概念。形态发生场的一个研究得最好的模型是早期青蛙胚胎的背腹(D-V)模式。这个模式系统受骨形态发生蛋白(BMP)信号通路和复杂的分泌蛋白拮抗剂网络的调节。相互作用蛋白的这种生化途径在细胞层在原肠胚形成期间进行广泛的形态发生运动时,在细胞外空间中起作用,以产生 BMP 信号的 D-V 梯度,该梯度在细胞层进行广泛的形态发生运动时得以维持。D-V 场分为背侧和腹侧中心,分别位于低和高 BMP 信号区域,在 BMP 的相反转录控制下。模式的稳健性通过两种不同的水平来保证。首先,在细胞外空间通过分泌 BMP 拮抗剂来实现,这些拮抗剂将 BMP 配体定向流向腹侧。这种流动是由 Chordin 抑制剂的调控蛋白水解以及腹侧存在的分子汇来驱动的,该分子汇集中了 BMP 信号。Tolloid 金属蛋白酶和 Chordin 结合蛋白 Crossveinless-2 (CV2) 是这个腹侧汇的关键成分。其次,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来调整其大小和 BMP 信号水平。这允许包含约 10000 个细胞的原肠胚一侧的细胞与胚胎相反极的细胞进行通信。

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