4.7 Article

The exocyst functions in niche cells to promote germline stem cell differentiation by directly controlling EGFR membrane trafficking

Journal

DEVELOPMENT
Volume 146, Issue 13, Pages -

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.174615

Keywords

EGFR; GSC; Differentiation; Exocyst; Niche; Stem cell; Drosophila; Human

Funding

  1. Tsinghua-Peking Joint Center for Life Sciences
  2. Ministry of Science and Technology of China [2013CB35102]
  3. National Natural Science Foundation of China [31371496, 31871421]
  4. Hong Kong Research Grants Council [26100315, 16101116, 16102218, AoE/M-05/12, C4002-17G]
  5. National Institutes of Health [R01HD097664]
  6. Stowers Institute for Medical Research

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The niche controls stem cell self-renewal and differentiation in animal tissues. Although the exocyst is known to be important for protein membrane trafficking and secretion, its role in stem cells and niches has never been reported. Here, this study shows that the exocyst functions in the niche to promote germline stem cell (GSC) progeny differentiation in the Drosophila ovary by directly regulating EGFR membrane trafficking and signaling. Inactivation of exocyst components in inner germarial sheath cells, which form the differentiation niche, causes a severe GSC differentiation defect. The exocyst is required for maintaining niche cells and preventing BMP signaling in GSC progeny by promoting EGFR membrane targeting and signaling through direct association with EGFR. Finally, it is also required for EGFR membrane targeting, recycling and signaling in human cells. Therefore, this study reveals a novel function of the exocyst in niche cells to promote stem cell progeny differentiation by directly controlling EGFR membrane trafficking and signaling in vivo, and also provides important insight into how the niche controls stem cell progeny differentiation at the molecular level.

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