Repression by PRDM13 is critical for generating precision in neuronal identity

Elife. 2017 Aug 29;6:e25787. doi: 10.7554/eLife.25787.

Abstract

The mechanisms that activate some genes while silencing others are critical to ensure precision in lineage specification as multipotent progenitors become restricted in cell fate. During neurodevelopment, these mechanisms are required to generate the diversity of neuronal subtypes found in the nervous system. Here we report interactions between basic helix-loop-helix (bHLH) transcriptional activators and the transcriptional repressor PRDM13 that are critical for specifying dorsal spinal cord neurons. PRDM13 inhibits gene expression programs for excitatory neuronal lineages in the dorsal neural tube. Strikingly, PRDM13 also ensures a battery of ventral neural tube specification genes such as Olig1, Olig2 and Prdm12 are excluded dorsally. PRDM13 does this via recruitment to chromatin by multiple neural bHLH factors to restrict gene expression in specific neuronal lineages. Together these findings highlight the function of PRDM13 in repressing the activity of bHLH transcriptional activators that together are required to achieve precise neuronal specification during mouse development.

Keywords: bHLH transcription factor; cell fate specification; chicken; developmental biology; dorsal neural tube; mouse; neuronal specification; stem cells.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Lineage / genetics
  • Chick Embryo
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Histone-Lysine N-Methyltransferase / genetics*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Interneurons / cytology
  • Interneurons / metabolism
  • Mice
  • Mice, Transgenic
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neural Tube / cytology
  • Neural Tube / growth & development
  • Neural Tube / metabolism
  • Neurogenesis / genetics*
  • Oligodendrocyte Transcription Factor 2 / genetics
  • Oligodendrocyte Transcription Factor 2 / metabolism
  • Signal Transduction
  • Spinal Cord / cytology
  • Spinal Cord / growth & development
  • Spinal Cord / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Nerve Tissue Proteins
  • Olig1 protein, mouse
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Prdm12 protein, mouse
  • Transcription Factors
  • Green Fluorescent Proteins
  • Prdm13 protein, mouse
  • Histone-Lysine N-Methyltransferase