MAZ mediates the cross-talk between CT-1 and NOTCH1 signaling during gliogenesis

Sci Rep. 2016 Feb 12:6:21534. doi: 10.1038/srep21534.

Abstract

Neurons and glia cells are differentiated from neural stem/progenitor cells (NSCs/NPCs) during brain development. Concomitant activation of JAK/STAT and NOTCH1 signaling is required for gliogenesis, a process to generate glia cells to ensure proper brain functions. NOTCH1 signaling is down-regulated during neurogenesis and up-regulated during gliogenesis. However, the underlying mechanism remains elusive. We report here that cardiotrophin-1 (CT-1) activates NOTCH1 signaling through the up-regulation of ADAM10, a rate-limiting factor of NOTCH1 signaling activation. We found that a transcriptional factor, Myc-associated zinc finger protein (MAZ), plays an important role in ADAM10 transcription in response to CT-1 in NPCs. MAZ knockdown inhibits CT-1 stimulated gliogenesis and it can be rescued by over-expressing human NICD. Our results provide a link between NOTCH1 activation and neuronal secreted CT-1, suggesting that CT-1 plays an important role in ensuring the coordinated activation of NOTCH1 signaling during gliogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM10 Protein / biosynthesis
  • ADAM10 Protein / genetics
  • Amyloid Precursor Protein Secretases / biosynthesis
  • Amyloid Precursor Protein Secretases / genetics
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Mice
  • NIH 3T3 Cells
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neuroglia / cytology
  • Neuroglia / metabolism*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Membrane Proteins
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Transcription Factors
  • c-MYC-associated zinc finger protein
  • cardiotrophin 1
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • ADAM10 protein, human