Department of Cell Biology, and Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China.
Zhejiang Provincial Key Laboratory of Genetic & Developmental Disorders, Zhejiang University School of Medicine, Hangzhou, 311121, China.
Nat Commun. 2022 May 20;13(1):2817. doi: 10.1038/s41467-022-30492-4.
Adult progenitor cells in the trachea of Drosophila larvae are activated and migrate out of niches when metamorphosis induces tracheal remodeling. Here we show that in response to metabolic deficiency in decaying tracheal branches, signaling by the insulin pathway controls the progenitor cells by regulating Yorkie (Yki)-dependent proliferation and migration. Yki, a transcription coactivator that is regulated by Hippo signaling, promotes transcriptional activation of cell cycle regulators and components of the extracellular matrix in tracheal progenitor cells. These findings reveal that regulation of Yki signaling by the insulin pathway governs proliferation and migration of tracheal progenitor cells, thereby identifying the regulatory mechanism by which metabolic depression drives progenitor cell activation and cell division that underlies tracheal remodeling.
当变形诱导气管重塑时,果蝇幼虫气管中的成体祖细胞被激活并从巢中迁移出来。在这里,我们表明,在对腐烂气管分支的代谢缺陷做出反应时,胰岛素途径的信号通过调节 Yorkie(Yki)依赖性增殖和迁移来控制祖细胞。Yki 是一种转录共激活因子,受 Hippo 信号调节,可促进细胞周期调节剂和气管祖细胞中细胞外基质成分的转录激活。这些发现表明,胰岛素途径对 Yki 信号的调节控制着气管祖细胞的增殖和迁移,从而确定了代谢抑制驱动祖细胞激活和细胞分裂的调节机制,这是气管重塑的基础。