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盘基网柄菌聚集体中细胞运动、细胞分化、细胞分选和比例调节的建模

Modelling cell movement, cell differentiation, cell sorting and proportion regulation in Dictyostelium discoideum aggregations.

作者信息

Pineda M, Weijer C J, Eftimie R

机构信息

Division of Mathematics, University of Dundee, Dundee DD1 4HN, United Kingdom.

School of Life Sciences, University of Dundee, Dundee DD1 4HN, United Kingdom.

出版信息

J Theor Biol. 2015 Apr 7;370:135-50. doi: 10.1016/j.jtbi.2015.01.042. Epub 2015 Feb 7.

Abstract

Understanding the mechanisms that control tissue morphogenesis and homeostasis is a central goal not only in developmental biology but also has great relevance for our understanding of various diseases, including cancer. A model organism that is widely used to study the control of tissue morphogenesis and proportioning is the Dictyostelium discoideum. While there are mathematical models describing the role of chemotactic cell motility in the Dictyostelium assembly and morphogenesis of multicellular tissues, as well as models addressing possible mechanisms of proportion regulation, there are no models incorporating both these key aspects of development. In this paper, we introduce a 1D hyperbolic model to investigate the role of two morphogens, DIF and cAMP, on cell movement, cell sorting, cell-type differentiation and proportioning in Dictyostelium discoideum. First, we use the non-spatial version of the model to study cell-type transdifferentiation. We perform a steady-state analysis of it and show that, depending on the shape of the differentiation rate functions, multiple steady-state solutions may occur. Then we incorporate spatial dynamics into the model, and investigate the transdifferentiation and spatial positioning of cells inside the newly formed structures, following the removal of prestalk or prespore regions of a Dictyostelium slug. We show that in isolated prespore fragments, a tipped mound-like aggregate can be formed after a transdifferentiation from prespore to prestalk cells and following the sorting of prestalk cells to the centre of the aggregate. For isolated prestalk fragments, we show the formation of a slug-like structure containing the usual anterior-posterior pattern of prestalk and prespore cells.

摘要

了解控制组织形态发生和体内平衡的机制不仅是发育生物学的核心目标,对于我们理解包括癌症在内的各种疾病也具有重要意义。盘基网柄菌是一种广泛用于研究组织形态发生和比例控制的模式生物。虽然有数学模型描述趋化性细胞运动在盘基网柄菌多细胞组织组装和形态发生中的作用,以及探讨比例调节可能机制的模型,但尚无同时纳入发育这两个关键方面的模型。在本文中,我们引入一个一维双曲模型来研究两种形态发生素DIF和cAMP在盘基网柄菌细胞运动、细胞分选、细胞类型分化和比例调节中的作用。首先,我们使用该模型的非空间版本来研究细胞类型的转分化。我们对其进行稳态分析,并表明根据分化速率函数的形状,可能会出现多个稳态解。然后我们将空间动力学纳入模型,并在去除盘基网柄菌蛞蝓体的前柄或前孢子区域后,研究新形成结构内细胞的转分化和空间定位。我们表明,在分离的前孢子片段中,从前孢子细胞转分化为前柄细胞并将前柄细胞分选到聚集体中心后,可以形成一个顶端呈丘状的聚集体。对于分离的前柄片段,我们展示了一种包含前柄和前孢子细胞通常前后模式的蛞蝓状结构的形成。

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