The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche

Dev Biol. 2012 Aug 15;368(2):181-92. doi: 10.1016/j.ydbio.2012.04.034. Epub 2012 May 8.

Abstract

Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAK-STAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Proliferation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Female
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • In Situ Hybridization
  • Male
  • Microscopy, Confocal
  • Mutation
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Stem Cell Niche / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Testis / cytology
  • Testis / growth & development
  • Testis / metabolism*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Ken protein, Drosophila
  • STAT Transcription Factors
  • Socs36E protein, Drosophila
  • Stat92E protein, Drosophila
  • Suppressor of Cytokine Signaling Proteins
  • Green Fluorescent Proteins
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Ptp61F protein, Drosophila