Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation

Cell Res. 2015 Oct;25(10):1152-70. doi: 10.1038/cr.2015.114. Epub 2015 Sep 25.

Abstract

Many stem cell populations are tightly regulated by their local microenvironment (niche), which comprises distinct types of stromal cells. However, little is known about mechanisms by which niche subgroups coordinately determine the stem cell fate. Here we identify that Yki, the key Hippo pathway component, is essential for escort cell (EC) function in promoting germline differentiation in Drosophila ovary. We found that Hedgehog (Hh) signals emanating primarily from cap cells support the function of ECs, where Cubitus interruptus (Ci), the Hh signaling effector, acts to inhibit Hippo kinase cascade activity. Mechanistically, we found that Ci competitively interacts with Hpo and impairs the Hpo-Wts signaling complex formation, thereby promoting Yki nuclear localization. The actions of Ci ensure effective Yki signaling to antagonize Sd/Tgi/Vg-mediated default repression in ECs. This study uncovers a mechanism explaining how subgroups of niche cells coordinate to determine the stem cell fate via Hh-Hippo signaling crosstalk, and enhances our understanding of mechanistic regulations of the oncogenic Yki/YAP signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism*
  • Drosophila / cytology*
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism*
  • Female
  • Germ Cells / cytology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Nuclear Proteins / metabolism
  • Ovary / cytology*
  • Ovary / growth & development
  • Protein Interaction Maps
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction*
  • Stem Cells / cytology*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • ci protein, Drosophila
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila