Department of Cell & Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
Department of Human Genetics, University of Utah, Salt Lake City, Utah, United States of America.
PLoS Genet. 2018 Jan 8;14(1):e1007146. doi: 10.1371/journal.pgen.1007146. eCollection 2018 Jan.
During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens.
在脊椎动物血管系统的发芽血管生成和果蝇气管系统的初级分支中，专门的尖端细胞指导分支生长和网络形成。当尖端细胞内腔化时，它们形成亚细胞（无缝）管。这些无缝管是如何形成、成型和维持的，仍然知之甚少。在这里，我们描述了一个名为 ichor（ich）的果蝇突变体，并表明 ich 对于气管末端细胞中无缝管的完整性和形状是必不可少的。我们发现 Ich 通过其在促进成熟的顶端细胞外基质（aECM）形成中的作用来调节无缝管的形成，该顶端细胞外基质排列在无缝管的腔中。我们确定 ich 编码一个锌指蛋白（CG11966），作为转录激活因子，对于多个 aECM 因子的表达是必需的，包括一种新型的膜锚定胰蛋白酶蛋白酶（CG8213）。因此，无缝管的完整性和形状受到排列在其腔中的 aECM 的调节。
