Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5329, USA; Institute for Genetics, University of Cologne, 50674 Cologne, Germany.
Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.
Stem Cell Reports. 2019 May 14;12(5):1024-1040. doi: 10.1016/j.stemcr.2019.03.008. Epub 2019 Apr 18.
Tissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate epidermal growth factor receptor (EGFR) signaling. Knockdown of dlg, scrib, lgl, or CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides insights into how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues.
组织稳态和修复依赖于干细胞及其分化后代与局部组织微环境的正确交流。在果蝇雄性生殖系成年干细胞谱系中，生殖细胞增殖并逐渐在支持性体腔细胞中分化，形成一个小的类器官，即分化的功能单位。在这里，我们表明细胞极性和囊泡运输影响囊腔细胞中的信号转导，对它们所包围的生殖细胞有深远的影响。我们的数据表明，皮质成分Dlg、Scrib、Lgl 和网格蛋白介导的内吞（CME）机制下调表皮生长因子受体（EGFR）信号。在囊腔细胞中敲低 dlg、scrib、lgl 或 CME 成分导致生殖细胞死亡，类似于通过 EGFR 增加信号转导，而降低 EGFR 或下游信号成分则挽救了缺陷。这项工作提供了关于细胞极性和内吞作用如何合作调节信号转导和塑造发育组织的见解。
