School of Life Sciences, Tsinghua University, Medical Science Building, D224, Beijing 100084, China.
School of Life Sciences, Tsinghua University, Medical Science Building, D224, Beijing 100084, China.
Dev Cell. 2017 Jul 10;42(1):97-106.e4. doi: 10.1016/j.devcel.2017.06.004.
Basement membranes (BMs) are extracellular matrix polymers basally underlying epithelia, where they regulate cell signaling and tissue mechanics. Constriction by the BM shapes Drosophila wing discs, a well-characterized model of tissue growth. Recently, the hypothesis that mechanical factors govern wing growth has received much attention, but it has not been definitively tested. In this study, we manipulated BM composition to cause dramatic changes in tissue tension. We found that increased tissue compression when perlecan was knocked down did not affect adult wing size. BM elimination, decreasing compression, reduced wing size but did not visibly affect Hippo signaling, widely postulated to mediate growth mechanoregulation. BM elimination, in contrast, attenuated signaling by bone morphogenetic protein/transforming growth factor β ligand Dpp, which was not efficiently retained within the tissue and escaped to the body cavity. Our results challenge mechanoregulation of wing growth, while uncovering a function of BMs in preserving a growth-promoting tissue environment.
基底膜（BMs）是位于上皮细胞底部的细胞外基质聚合物，调节细胞信号和组织力学。BM 的收缩塑造了果蝇翅膀盘，这是一个组织生长的良好模型。最近，机械因素控制翅膀生长的假设引起了广泛关注，但尚未得到明确验证。在这项研究中，我们操纵 BM 组成以引起组织张力的剧烈变化。我们发现，当 perlecan 被敲低时，组织压缩增加并没有影响成年翅膀的大小。BM 的消除，即压缩减少，会减小翅膀的大小，但不会明显影响 Hippo 信号通路，该信号通路被广泛假设为介导生长的机械调节。相比之下，BM 的消除会削弱骨形态发生蛋白/转化生长因子 β 配体 Dpp 的信号，该配体不能有效地保留在组织内并逃到体腔。我们的结果挑战了翅膀生长的机械调节，同时揭示了 BM 在维持促进生长的组织环境方面的功能。
