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原肠胚形成过程中的物理化学机制。

Physical-chemical mechanisms of pattern formation during gastrulation.

机构信息

Department of Chemistry and Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005-1892, USA.

Department of Physics and FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

出版信息

J Chem Phys. 2018 Mar 28;148(12):123302. doi: 10.1063/1.4993879.

Abstract

Gastrulation is a fundamental phase during the biological development of most animals when a single layer of identical embryo cells is transformed into a three-layer structure, from which the organs start to develop. Despite a remarkable progress in quantifying the gastrulation processes, molecular mechanisms of these processes remain not well understood. Here we theoretically investigate early spatial patterning in a geometrically confined colony of embryonic stem cells. Using a reaction-diffusion model, a role of Bone-Morphogenetic Protein 4 (BMP4) signaling pathway in gastrulation is specifically analyzed. Our results show that for slow diffusion rates of BMP4 molecules, a new length scale appears, which is independent of the size of the system. This length scale separates the central region of the colony with uniform low concentrations of BMP molecules from the region near the colony edge where the concentration of signaling molecules is elevated. The roles of different components of the signaling pathway are also explained. Theoretical results are consistent with recent in vitro experiments, providing microscopic explanations for some features of early embryonic spatial patterning. Physical-chemical mechanisms of these processes are discussed.

摘要

原肠作用是大多数动物在生物学发育过程中的一个基本阶段,在此过程中,单层相同的胚胎细胞转变为三层结构,器官开始发育。尽管在量化原肠作用过程方面取得了显著进展,但这些过程的分子机制仍未得到很好的理解。在这里,我们从理论上研究了胚胎干细胞在几何约束的群体中的早期空间模式。使用反应扩散模型,特别分析了骨形态发生蛋白 4 (BMP4)信号通路在原肠作用中的作用。我们的结果表明,对于 BMP4 分子的缓慢扩散速率,会出现一个新的长度尺度,该长度尺度与系统的大小无关。该长度尺度将具有均匀低浓度 BMP 分子的群体中心区域与群体边缘附近的信号分子浓度升高的区域分隔开来。还解释了信号通路的不同组成部分的作用。理论结果与最近的体外实验一致,为早期胚胎空间模式形成的一些特征提供了微观解释。还讨论了这些过程的物理化学机制。

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