Spatial, temporal and molecular hierarchies in the link between death, delamination and dorsal closure
Spatial, temporal and molecular hierarchies in the link between death, delamination and dorsal closure
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DOI：
10.1242/dev.060731
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发表时间：
2011-07-15
期刊：
影响因子：
4.6
通讯作者：
Narasimha, Maithreyi
中科院分区：
文献类型：
--
作者：
Muliyil, Sonia;Krishnakumar, Pritesh;Narasimha, Maithreyi
大多数上皮细胞中的死亡细胞通过细胞挤压而被消除。在这里，我们探讨羊膜浆膜中的细胞分层（一种看似随机的事件，导致一小部分细胞挤出并已知为背侧闭合提供力）是否取决于细胞凋亡信号的接收。通过对突变体组合的分析和原位凋亡信号的分析，我们建立了死亡和分层之间联系的空间、时间和分子层次结构。我们表明，尽管细胞凋亡信号对于提供分层的细胞自主指令是必要且充分的，但在自然分层过程中其诱导发生在线粒体断裂的下游。我们进一步表明，凋亡调节因子可以非自主地影响分层和背侧闭合细胞，大概是通过影响组织力学。分层频率和线粒体形态的空间异质性表明机械应力可能通过影响线粒体动力学而成为凋亡级联激活的基础。我们的结果首次记录了细胞凋亡信号在发育过程中完成形态发生的细胞行为背景下的时间传播。他们强调了线粒体动力学和组织力学在其调节中的重要性。它们共同为如何将细胞凋亡信号应用于组织模式提供了新的见解。
Dead cells in most epithelia are eliminated by cell extrusion. Here, we explore whether cell delamination in the amnioserosa, a seemingly stochastic event that results in the extrusion of a small fraction of cells and known to provide a force for dorsal closure, is contingent upon the receipt of an apoptotic signal. Through the analysis of mutant combinations and the profiling of apoptotic signals in situ, we establish spatial, temporal and molecular hierarchies in the link between death and delamination. We show that although an apoptotic signal is necessary and sufficient to provide cell-autonomous instructions for delamination, its induction during natural delamination occurs downstream of mitochondrial fragmentation. We further show that apoptotic regulators can influence both delamination and dorsal closure cell non-autonomously, presumably by influencing tissue mechanics. The spatial heterogeneities in delamination frequency and mitochondrial morphology suggest that mechanical stresses may underlie the activation of the apoptotic cascade through their influence on mitochondrial dynamics. Our results document for the first time the temporal propagation of an apoptotic signal in the context of cell behaviours that accomplish morphogenesis during development. They highlight the importance of mitochondrial dynamics and tissue mechanics in its regulation. Together, they provide novel insights into how apoptotic signals can be deployed to pattern tissues.