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Vsx1 and Chx10 paralogs sequentially secure V2 interneuron identity during spinal cord development
Cellular and Molecular Life Sciences ( IF 8 ) Pub Date : 2019-12-10 , DOI: 10.1007/s00018-019-03408-7
Stéphanie Debrulle , Charlotte Baudouin , Maria Hidalgo-Figueroa , Barbara Pelosi , Cédric Francius , Vincent Rucchin , Kara Ronellenfitch , Robert L. Chow , Fadel Tissir , Soo-Kyung Lee , Frédéric Clotman

Paralog factors are usually described as consolidating biological systems by displaying redundant functionality in the same cells. Here, we report that paralogs can also cooperate in distinct cell populations at successive stages of differentiation. In mouse embryonic spinal cord, motor neurons and V2 interneurons differentiate from adjacent progenitor domains that share identical developmental determinants. Therefore, additional strategies secure respective cell fate. In particular, Hb9 promotes motor neuron identity while inhibiting V2 differentiation, whereas Chx10 stimulates V2a differentiation while repressing motor neuron fate. However, Chx10 is not present at the onset of V2 differentiation and in other V2 populations. In the present study, we show that Vsx1, the single paralog of Chx10, which is produced earlier than Chx10 in V2 precursors, can inhibit motor neuron differentiation and promote V2 interneuron production. However, the single absence of Vsx1 does not impact on V2 fate consolidation, suggesting that lack of Vsx1 may be compensated by other factors. Nevertheless, Vsx1 cooperates with Chx10 to prevent motor neuron differentiation in early V2 precursors although these two paralog factors are not produced in the same cells. Hence, this study uncovers an original situation, namely labor division, wherein paralog genes cooperate at successive steps of neuronal development.

中文翻译:

Vsx1和Chx10旁系同源物在脊髓发育过程中顺序确保V2间神经元身份

通常将旁系同源因子描述为通过在同一细胞中显示冗余功能来巩固生物系统。在这里,我们报告旁系同源物也可以在分化的连续阶段在不同的细胞群体中合作。在小鼠胚胎脊髓中,运动神经元和V2神经元与共享相同发育决定子的相邻祖细胞域区分开。因此,其他策略可确保各自的细胞命运。特别是,Hb9在抑制V2分化的同时促进运动神经元的识别,而Chx10在抑制运动神经元的命运的同时刺激V2a的分化。但是,Chx10在V2分化开始和其他V2群体中不存在。在本研究中,我们显示了Vsx1,即Chx10的单个旁系同源物,它比V2前体中的Chx10早产生,可以抑制运动神经元分化并促进V2中间神经元的产生。但是,仅缺少Vsx1不会影响V2的命运整合,这表明其他因素可能会弥补Vsx1的不足。尽管如此,Vsx1与Chx10协作以防止早期V2前体中的运动神经元分化,尽管这两个旁系同源因子不是在同一细胞中产生的。因此,本研究揭示了一种原始情况,即分工,其中旁系同源基因在神经元发育的连续步骤中协同作用。Vsx1与Chx10合作,以防止早期V2前体中的运动神经元分化,尽管这两个旁系同源因子不在同一细胞中产生。因此,本研究揭示了一种原始情况,即分工,其中旁系同源基因在神经元发育的连续步骤中协同作用。Vsx1与Chx10合作,以防止早期V2前体中的运动神经元分化,尽管这两个旁系同源因子不在同一细胞中产生。因此,本研究揭示了一种原始情况,即分工,其中旁系同源基因在神经元发育的连续步骤中协同作用。
更新日期:2019-12-11
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