Nf2-Yap signaling controls the expansion of DRG progenitors and glia during DRG development

Dev Biol. 2015 Feb 1;398(1):97-109. doi: 10.1016/j.ydbio.2014.11.017. Epub 2014 Nov 26.

Abstract

Molecular mechanisms governing the maintenance and proliferation of dorsal root ganglia (DRG) progenitors are largely unknown. Here we reveal that the Hippo pathway regulates the expansion of DRG progenitors and glia during mammalian DRG development. The key effectors of this pathway, transcriptional coactivators Yap and Taz, are expressed in DRG progenitors and glia during DRG development but are at least partially inhibited from activating transcription. Aberrant YAP activation leads to overexpansion of DRG progenitor and glial populations. We further show that the Neurofibromatosis 2 (Nf2) tumor suppressor inhibits Yap during DRG development. Loss of Nf2 leads to similar phenotypes as does YAP hyperactivation, and deleting Yap suppresses these phenotypes. Our study demonstrates that Nf2-Yap signaling plays important roles in controlling the expansion of DRG progenitors and glia during DRG development.

Keywords: Neural crest; Satellite glia; Sensory neurons; The peripheral nervous system.

Publication types

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

MeSH terms

  • Acyltransferases
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Proteins
  • Cell Movement
  • Ganglia, Spinal / embryology*
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Genes, Neurofibromatosis 2
  • Genes, Tumor Suppressor
  • Hippo Signaling Pathway
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Neurofibromin 2 / metabolism*
  • Neuroglia / cytology*
  • Neuroglia / metabolism
  • Phenotype
  • Phosphoproteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction*
  • Stem Cells / cytology*
  • Time Factors
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Neurofibromin 2
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Acyltransferases
  • tafazzin protein, mouse
  • Protein Serine-Threonine Kinases