In the developing neural tube in chicken and mammals, neural stem cells proliferate and differentiate according to a stereotyped spatiotemporal pattern. Several actors have been identified in the control of this process, from tissue-scale morphogens patterning to intrinsic determinants in neural progenitor cells. In a previous study (Bonnet et al. eLife 7, 2018), we have shown that the CDC25B phosphatase promotes the transition from proliferation to differentiation by stimulating neurogenic divisions, suggesting that it acts as a maturating factor for neural progenitors. In this previous study, we set up a mathematical model linking fixed progenitor modes of division to the dynamics of progenitors and differentiated populations. Here, we extend this model over time to propose a complete dynamical picture of this process. We start from the standard paradigm that progenitors are homogeneous and can perform any type of divisions (proliferative division yielding two progenitors, asymmetric neurogenic divisions yielding one progenitor and one neuron, and terminal symmetric divisions yielding two neurons). We calibrate this model using data published by Saade et al. (Cell Reports 4, 2013) about mode of divisions and population dynamics of progenitors/neurons at different developmental stages. Next, we explore the scenarios in which the progenitor population is actually split into two different pools, one of which is composed of cells that have lost the capacity to perform proliferative divisions. The scenario in which asymmetric neurogenic division would induce such a loss of proliferative capacity appears very relevant.

中文翻译：

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用神经祖细胞失去增殖能力来定时脊髓发育：理论分析。

在成年鸡和哺乳动物的神经管中，神经干细胞根据刻板的时空模式增殖和分化。从组织规模的形态发生素到神经祖细胞中的内在决定因素，已经确定了几种控制该过程的因子。在先前的研究中（Bonnet et al.eLife 7，2018），我们已经证明CDC25B磷酸酶通过刺激神经源性分裂来促进从增殖到分化的转变，表明它是神经祖细胞的成熟因子。在之前的研究中，我们建立了一个数学模型，将固定的祖细胞分裂模式与祖细胞和分化种群的动力学联系起来。在这里，我们随着时间的推移扩展了该模型，以提供此过程的完整动态图。我们从祖先是同质的并且可以执行任何类型的分裂的标准范例开始（增殖分裂产生两个祖细胞，非对称神经源分裂产生一个祖细胞和一个神经元，终末对称分裂产生两个神经元）。我们使用Saade等人发布的数据校准该模型。（Cell Reports 4，2013）有关祖细胞/神经元在不同发育阶段的分裂方式和种群动态的信息。接下来，我们探讨了将祖细胞实际上分为两个不同池的情况，其中一个池由失去执行增殖分裂能力的细胞组成。不对称神经源性分裂会引起这种增殖能力丧失的情况似乎非常相关。