The Hippo pathway regulates homeostatic growth of stem cell niche precursors in the Drosophila ovary

PLoS Genet. 2015 Feb 2;11(2):e1004962. doi: 10.1371/journal.pgen.1004962. eCollection 2015 Feb.

Abstract

The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Germ Cells / cytology
  • Germ Cells / growth & development*
  • Homeostasis / genetics
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Ovary / growth & development
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Interference
  • Receptors, Invertebrate Peptide / genetics
  • Receptors, Invertebrate Peptide / metabolism
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Stem Cell Niche / genetics*

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Invertebrate Peptide
  • STAT Transcription Factors
  • Egfr protein, Drosophila
  • ErbB Receptors
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila