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进化工程与脊椎动物脊髓的细胞和分子起源

Evo-engineering and the cellular and molecular origins of the vertebrate spinal cord.

作者信息

Steventon Ben, Martinez Arias Alfonso

机构信息

Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.

出版信息

Dev Biol. 2017 Dec 1;432(1):3-13. doi: 10.1016/j.ydbio.2017.01.021. Epub 2017 Feb 10.

Abstract

The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate them to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development.

摘要

在脊椎动物胚胎的早期胚胎发育过程中,脊髓的形成是一个连续的过程,始于原肠胚形成期,并持续到体节发生完成。尽管在生成特定脊髓祖细胞时模式形成机制和基因调控网络的使用具有保守性,但现在存在两种看似不同的模型来解释它们的作用。在第一种模型中,一个位于后部的信号源将先前指定为前部的神经板转化为脊髓。在第二种模型中,一群双能干细胞进行持续的自我更新和分化,通过后部生长逐渐形成脊髓和轴向中胚层。这是否代表了用于生成这些模型的实验模式生物之间的根本差异仍有待探讨。在这里,我们回顾了四种关键脊椎动物模型(小鼠、鸡、非洲爪蟾和斑马鱼)的谱系研究,并将它们与已知的脊髓形成所需的潜在基因调控网络联系起来。我们提出,通过应用动态系统方法来理解不同的神经和中胚层命运是如何从双能祖细胞库中产生的,就有可能开始理解诸如增殖率和细胞运动等动态细胞行为的差异如何映射到保守的调控网络上,从而在发育过程中产生组织生成和模式形成时间上的多样性。

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