Cytokinetic Abscission Regulation in Neural Stem Cells and Tissue Development.
Cytokinetic Abscission Regulation in Neural Stem Cells and Tissue Development.
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DOI：
10.1007/s40778-021-00193-7
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发表时间：
2021-12
影响因子：
1.4
通讯作者：
Dwyer, Noelle D
中科院分区：
文献类型：
--
作者：
McNeely, Katrina C;Dwyer, Noelle D
干细胞如何平衡增殖和分化，在发育过程中产生特定的子细胞来构建胚胎或组织，仍然是一个悬而未决的问题。在这里，我们讨论最近的证据表明，干细胞，特别是神经干细胞(NSCs)中的细胞动力学脱落调节是答案的一部分。脱落是一个由中体介导的多步骤过程，中体是有丝分裂后在子细胞之间的细胞间桥中形成的以微管为基础的结构。人类脱落基因的突变和老鼠的敲除表明，NSC脱落的细微中断可能会导致大脑畸形。在几个上皮系统中的实验表明，中体作为顶端连接蛋白的支架，位于顶膜命运决定因素附近。脱落时间在干细胞中受到严格控制和发育调节，在早期胚胎中延迟脱落，在以后更快地脱落。中体残留物(MBR)含有400多种蛋白质，可能影响极性、命运和纤毛发生。当神经干细胞和其他干细胞构建组织时，它们严格控制脱落的三个方面：中体位置、持续时间和MBR处理。中体位置和残留物建立或维持细胞的极性。MBR沉积在上皮细胞的顶膜上，可以被周围细胞释放或内化，并可能隔离命运决定因素或在细胞之间传递信息。在细胞系和更简单的系统中的研究表明，脱落调节在发育过程中影响干细胞的极性、效力和子代命运的多重作用。阐明脱落过程如何影响细胞命运和组织生长，对于我们继续了解大脑发育和干细胞生物学是很重要的。
How stem cells balance proliferation with differentiation, giving rise to specific daughter cells during development to build an embryo or tissue, remains an open question. Here, we discuss recent evidence that cytokinetic abscission regulation in stem cells, particularly neural stem cells (NSCs), is part of the answer. Abscission is a multi-step process mediated by the midbody, a microtubule-based structure formed in the intercellular bridge between daughter cells after mitosis. Human mutations and mouse knockouts in abscission genes reveal that subtle disruptions of NSC abscission can cause brain malformations. Experiments in several epithelial systems have shown that midbodies serve as scaffolds for apical junction proteins and are positioned near apical membrane fate determinants. Abscission timing is tightly controlled and developmentally regulated in stem cells, with delayed abscission in early embryos and faster abscission later. Midbody remnants (MBRs) contain over 400 proteins and may influence polarity, fate, and ciliogenesis. As NSCs and other stem cells build tissues, they tightly regulate three aspects of abscission: midbody positioning, duration, and MBR handling. Midbody positioning and remnants establish or maintain cell polarity. MBRs are deposited on the apical membranes of epithelia, can be released or internalized by surrounding cells, and may sequester fate determinants or transfer information between cells. Work in cell lines and simpler systems has shown multiple roles for abscission regulation influencing stem cell polarity, potency, and daughter fates during development. Elucidating how the abscission process influences cell fate and tissue growth is important for our continued understanding of brain development and stem cell biology.