Maintenance of Drosophila germline stem cell sexual identity in oogenesis and tumorigenesis

Development
Laura Shapiro-KulnaneHelen K Salz

Abstract

Adult stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. In Drosophila females, germline stem cells (GSCs) require Sex lethal (Sxl) to exit the stem cell state and to enter the differentiation pathway. Without Sxl GSCs do not differentiate and instead form tumors. Previous studies have shown that these tumors are not caused by a failure in the self-renewal/differentiation switch. Here, we show that Sxl is also necessary for the cell-autonomous maintenance of germ cell female identity and demonstrate that tumors are caused by the acquisition of male characteristics. Germ cells without Sxl protein exhibit a global derepression of testis genes, including Phf7, a male germline sexual identity gene. Phf7 is a key effector of the tumor-forming pathway, as it is both necessary and sufficient for tumor formation. In the absence of Sxl protein, inappropriate Phf7 expression drives tumor formation through a cell-autonomous mechanism that includes sex-inappropriate activation of Jak/Stat signaling. Remarkably, tumor formation requires a novel response to external signals emanating from the GSC niche, highlighting the importance of interactions between mutant cells and the surrounding normal cells that ma...Continue Reading

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Citations

Sep 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Dong Yan, Norbert Perrimon
Jan 13, 2017·Molecular Reproduction and Development·Helen K SalzJason D Heaney
Jul 5, 2017·Nature Communications·Lijuan KanEric C Lai
Mar 23, 2018·Human Molecular Genetics·Anlu ChenDavid A Buchner
Dec 19, 2017·Frontiers in Endocrinology·Kate L LovelandHans-Christian Schuppe
May 1, 2019·Proceedings of the National Academy of Sciences of the United States of America·Hiroki SakaiTeruyuki Niimi
Nov 11, 2017·Development, Growth & Differentiation·Ryoma OtaSatoru Kobayashi
May 26, 2017·Proceedings. Biological Sciences·Xin Rui WangShu Yuan Yang
Oct 10, 2018·Nature Communications·Anne E SmolkoHelen K Salz

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