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A Notch-mediated temporal asymmetry in BMP pathway activation promotes photoreceptor subtype diversification

机译:Notch介导的BMP途径激活中的时间不对称促进了感光受体亚型的多样化

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摘要

Neural progenitors produce neurons whose identities can vary as a function of the time that specification occurs. Here, we describe the heterochronic specification of two photoreceptor (PhR) subtypes in the zebrafish pineal gland. We find that accelerating PhR specification by impairing Notch signaling favors the early fate at the expense of the later fate. Using in vivo lineage tracing, we show that most pineal PhRs are born from a fate-restricted progenitor. Furthermore, sister cells derived from the division of PhR-restricted progenitors activate the bone morphogenetic protein (BMP) signaling pathway at different times after division, and this heterochrony requires Notch activity. Finally, we demonstrate that PhR identity is established as a function of when the BMP pathway is activated. We propose a novel model in which division of a progenitor with restricted potential generates sister cells with distinct identities via a temporal asymmetry in the activation of a signaling pathway.
机译:神经祖细胞产生神经元,其身份可以随特定时间的变化而变化。在这里,我们描述了斑马鱼松果体中两个感光体(PhR)亚型的异时性规范。我们发现通过削弱Notch信号来加快PhR指标有利于早期命运,但会损害后期命运。使用体内谱系追踪,我们显示大多数松果体PhR都来自命运受限的祖先。此外,源自PhR限制性祖细胞分裂的姐妹细胞在分裂后的不同时间激活骨形态发生蛋白(BMP)信号传导途径,并且这种异质性需要Notch活性。最后,我们证明了PhR身份随BMP途径被激活而建立。我们提出了一种新颖的模型,其中具有有限潜力的祖细胞的分裂通过信号通路激活中的时间不对称性产生具有不同身份的姊妹细胞。

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