Francis Deanne, Ghabrial Amin S
Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Development. 2015 Jun 1;142(11):2048-57. doi: 10.1242/dev.119602. Epub 2015 May 14.
Tubes are essential for nutrient transport and gas exchange in multicellular eukaryotes, but how connections between different tube types are maintained over time is unknown. In the Drosophila tracheal system, mutations in oak gall (okg) and conjoined (cnj) confer identical defects, including late onset blockage near the terminal cell-stalk cell junction and the ectopic extension of autocellular, seamed tubes into the terminal cell. We determined that okg and cnj encode the E and G subunits of the vacuolar ATPase (vATPase) and showed that both the V0 and V1 domains are required for terminal cell morphogenesis. Remarkably, the ectopic seamed tubes running along vATPase-deficient terminal cells belonged to the neighboring stalk cells. All vATPase-deficient tracheal cells had reduced apical domains and terminal cells displayed mislocalized apical proteins. Consistent with recent reports that the mTOR and vATPase pathways intersect, we found that mTOR pathway mutants phenocopied okg and cnj. Furthermore, terminal cells depleted for the apical determinants Par6 or aPKC had identical ectopic seamed tube defects. We thus identify a novel mechanism of compensatory branching in which stalk cells extend autocellular tubes into neighboring terminal cells with undersized apical domains. This compensatory branching also occurs in response to injury, with damaged terminal cells being rapidly invaded by their stalk cell neighbor.
管道对于多细胞真核生物中的营养物质运输和气体交换至关重要，但不同类型管道之间的连接如何随时间维持尚不清楚。在果蝇气管系统中，橡树瘿（okg）和连体（cnj）的突变会导致相同的缺陷，包括终末细胞-柄细胞连接处附近的迟发性阻塞以及自细胞、有接缝的管道异位延伸至终末细胞。我们确定okg和cnj编码液泡ATP酶（vATP酶）的E和G亚基，并表明V0和V1结构域对于终末细胞形态发生都是必需的。值得注意的是，沿着vATP酶缺陷型终末细胞延伸的异位有接缝管道属于相邻的柄细胞。所有vATP酶缺陷型气管细胞的顶端结构域都减小，终末细胞显示顶端蛋白定位错误。与最近关于mTOR和vATP酶途径相交的报道一致，我们发现mTOR途径突变体表现出与okg和cnj相似的表型。此外，顶端决定因子Par6或非典型蛋白激酶C（aPKC）缺失的终末细胞具有相同的异位有接缝管道缺陷。因此，我们确定了一种新的补偿性分支机制，即柄细胞将自细胞管道延伸到顶端结构域过小的相邻终末细胞中。这种补偿性分支也会在受到损伤时发生，受损的终末细胞会迅速被其相邻的柄细胞侵入。
