Institute of Zoology, Universität Zürich, CH-8057 Zürich, Switzerland.
Curr Biol. 2010 Jan 12;20(1):62-8. doi: 10.1016/j.cub.2009.11.062. Epub 2009 Dec 31.
Epithelial tubes in developing organs, such as mammalian lungs and insect tracheae, need to expand their initially narrow lumina to attain their final, functional dimensions. Despite its critical role for organ function, the cellular mechanism of tube expansion remains unclear. Tracheal tube expansion in Drosophila involves apical secretion and deposition of a luminal matrix, but the mechanistic role of secretion and the nature of forces involved in the process were not previously clear. Here we address the roles of cell-intrinsic and extrinsic processes in tracheal tube expansion. We identify mutations in the sec24 gene stenosis, encoding a cargo-binding subunit of the COPII complex. Via genetic-mosaic analyses, we show that stenosis-dependent secretion drives tube expansion in a cell-autonomous fashion. Strikingly, single cells autonomously adjust both tube diameter and length by implementing a sequence of events including apical membrane growth, cell flattening, and taenidial cuticle formation. Known luminal components are not required for this process. Thus, a cell-intrinsic program, rather than nonautonomous extrinsic cues, controls the dimensions of tracheal tubes. These results indicate a critical role of membrane-associated proteins in the process and imply a mechanism that coordinates autonomous behaviors of individual cells within epithelial structures.
在发育器官中，上皮管需要扩大最初狭窄的腔以达到最终的功能尺寸，例如哺乳动物的肺和昆虫的气管。尽管这对器官功能至关重要，但管腔扩张的细胞机制仍不清楚。果蝇气管管腔的扩张涉及顶端分泌和管腔基质的沉积，但分泌的力学作用和过程中涉及的力的性质以前并不清楚。在这里，我们研究了细胞内和细胞外过程在气管管腔扩张中的作用。我们鉴定了编码 COPII 复合物货物结合亚基 sec24 基因 stenosis 的突变。通过遗传嵌合分析，我们表明stenosis 依赖性分泌以细胞自主的方式驱动管腔扩张。引人注目的是，单个细胞通过实施包括顶膜生长、细胞变平以及 taenidial 角质层形成在内的一系列事件，自主调节管腔的直径和长度。这个过程不需要已知的腔内容物。因此，细胞内在程序而不是非自主的外在线索控制气管管腔的尺寸。这些结果表明膜相关蛋白在该过程中起着关键作用，并暗示了一种协调上皮结构内单个细胞自主行为的机制。
