University of Nottingham, University Park, UK.
J Theor Biol. 2009 Sep 7;260(1):41-55. doi: 10.1016/j.jtbi.2009.05.016. Epub 2009 May 31.
In this paper we develop a model of mesendoderm specification in Xenopus laevis based on an existing gene regulation network. The mesendoderm is a population of cells that may contribute to either the mesoderm or endoderm. The model that we develop encompasses the time evolution of transcription factor concentrations in a single cell and is shown to have stable steady states that correspond to mesoderm and anterior mesendodermal cell types, but not endoderm (except in cells where Goosecoid expression is inhibited). Both in vitro and in vivo versions of the model are developed and analysed, the former indicating how cell fate is determined in large part by the concentration of Activin administered to a cell, with the model results comparing favourably with current quantitative experimental data. A numerical investigation of the in vivo model suggests that cell fate is determined largely by a VegT and beta-Catenin pre-pattern, subsequently being reinforced by Nodal. We argue that this sensitivity of the model to a VegT and beta-Catenin pre-pattern indicates that a key VegT self-limiting mechanism (for which there is experimental evidence) is absent from the model. Furthermore, we find that the lack of a steady state corresponding to endoderm is entirely consistent with current in vivo data, and that the in vivo model corresponds to mesendoderm specification on the dorsal, but not the ventral, side of the embryo.
本文基于现有的基因调控网络，建立了非洲爪蟾中中胚层特化的模型。中胚层是一群可能分化为中胚层或内胚层的细胞。我们开发的模型涵盖了单个细胞中转录因子浓度的时间演化，并显示出稳定的稳定状态，这些状态对应于中胚层和前中胚层细胞类型，但不对应于内胚层（除非在抑制 Goosecoid 表达的细胞中）。该模型的体外和体内版本均得到了开发和分析，前者表明细胞命运在很大程度上取决于给予细胞的 Activin 浓度，模型结果与当前的定量实验数据非常吻合。对体内模型的数值研究表明，细胞命运主要由 VegT 和β-连环蛋白的预图案决定，随后由 Nodal 加强。我们认为，模型对 VegT 和β-连环蛋白预图案的敏感性表明，模型中缺少一个关键的 VegT 自我限制机制（有实验证据支持）。此外，我们发现，缺乏与内胚层相对应的稳定状态与当前的体内数据完全一致，并且体内模型对应于胚胎背侧而不是腹侧的中胚层特化。
