The actomyosin machinery is required for Drosophila retinal lumen formation.
The actomyosin machinery is required for Drosophila retinal lumen formation.
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DOI：
10.1371/journal.pgen.1004608
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发表时间：
2014-09
期刊：
影响因子：
4.5
通讯作者：
Zelhof AC
中科院分区：
文献类型：
--
作者：
Nie J;Mahato S;Zelhof AC
多细胞管由围绕中心腔的极化细胞组成，是许多发育和生理功能的基础结构。在果蝇复眼中，每个小眼形成一个管腔基质，即横纹肌间空间，以形成和分离关键的光转导细胞器，即横纹肌，以获得适当的视觉感知。在增强子筛选以确定视网膜管腔形成的机制中，我们将Actin5C鉴定为关键分子。我们的研究结果表明，破坏后减少肌动蛋白5C的管腔形成是没有任何明显的缺陷，在微绒毛形成，横纹肌末端网（RTW），或整体形态发生和基底延伸的横纹肌。其次，正常管腔形成的失败不是先前确定的视网膜管腔形成过程的结果：Prominin定位，顶膜扩张或管腔基质分泌。相反，在非肌肉肌球蛋白II（MyoII）及其上游激活剂的单个组分减少时，用Actin5C观察到的表型被表型化。在光感受器细胞中，MyoII定位于横纹肌的基部，与RTW的肌动蛋白丝重叠。与肌动球蛋白介导的细胞收缩的既定滚动一致，MyoII的减少导致顶端膜之间的距离减少，如通过管腔直径的减少所测量的。总之，我们的研究结果表明，肌动球蛋白机制与顶膜成分的定位和细胞外基质的分泌相协调，以克服顶膜粘附，从而启动和扩大视网膜内腔。生物管道是组织和器官如肺、肾和心血管系统的完整单元。管子的基本设计包括一个被一层细胞包裹的中央腔。为了正常发挥作用，这些管需要精确的遗传控制它们的创造，直径生长和发育过程中管腔的维持。在果蝇（Drosophila melanogaster）中，眼睛的感光细胞形成管状结构。视网膜腔的形成对于分离和定位每个感光细胞的感光细胞器以实现视觉灵敏度至关重要。为了研究果蝇视网膜管腔形成的机制，我们确定了一种存在于感光细胞顶端的收缩机制。我们的数据是一致的想法，即收缩力有助于最初的分离并列顶端膜和随后扩大的管腔空间。我们的工作表明，建立一个生物管不仅需要一个外在的推力提供的不断增长的中央管腔，但也有一个细胞内在的拉力由收缩的细胞内衬管腔。我们的研究结果扩展并证明了几种分子机制的协调，以产生一个管。
Multicellular tubes consist of polarized cells wrapped around a central lumen and are essential structures underlying many developmental and physiological functions. In Drosophila compound eyes, each ommatidium forms a luminal matrix, the inter-rhabdomeral space, to shape and separate the key phototransduction organelles, the rhabdomeres, for proper visual perception. In an enhancer screen to define mechanisms of retina lumen formation, we identified Actin5C as a key molecule. Our results demonstrate that the disruption of lumen formation upon the reduction of Actin5C is not linked to any discernible defect in microvillus formation, the rhabdomere terminal web (RTW), or the overall morphogenesis and basal extension of the rhabdomere. Second, the failure of proper lumen formation is not the result of previously identified processes of retinal lumen formation: Prominin localization, expansion of the apical membrane, or secretion of the luminal matrix. Rather, the phenotype observed with Actin5C is phenocopied upon the decrease of the individual components of non-muscle myosin II (MyoII) and its upstream activators. In photoreceptor cells MyoII localizes to the base of the rhabdomeres, overlapping with the actin filaments of the RTW. Consistent with the well-established roll of actomyosin-mediated cellular contraction, reduction of MyoII results in reduced distance between apical membranes as measured by a decrease in lumen diameter. Together, our results indicate the actomyosin machinery coordinates with the localization of apical membrane components and the secretion of an extracellular matrix to overcome apical membrane adhesion to initiate and expand the retinal lumen. Biological tubes are integral units of tissues and organs such as lung, kidney, and the cardiovascular system. The fundamental design of tubes involves a central lumen wrapped by a sheet of cells. To function properly, the tubes require a precise genetic control over their creation, the diametric growth and maintenance of the lumen during development. In the fruit fly, Drosophila melanogaster, the photoreceptor cells of the eye form a tubular structure. The formation of the retinal lumen is critical for separating and positioning the light sensing organelles of each photoreceptor cell to achieve visual sensitivity. In an effort to investigate the mechanisms of Drosophila retinal lumen formation, we identified a contractile machinery that was present at the apical portion of photoreceptor cells. Our data is consistent with the idea that a contractile force contributes to the initial separation of the juxtaposed apical membranes and subsequent enlargement of the luminal space. Our work suggests that building a biological tube requires not only an extrinsic pushing force provided by the growing central lumen, but also a cell intrinsic pulling force powered by contraction of cells lining the lumen. Our findings expand and demonstrate the coordination of several molecular mechanisms to generate a tube.
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