The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification

Dev Biol. 2016 Aug 15;416(2):361-72. doi: 10.1016/j.ydbio.2016.06.012. Epub 2016 Jun 23.

Abstract

Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a 'gate-keeper' for the correct temporal and spatial development of the neural crest.

Keywords: Cdk9; CyclinT1; Leflunomide; Neural crest cells; P-TEFb; Polymerase pausing; Transcriptional elongation; Xenopus; c-Myc.

MeSH terms

  • Animals
  • Cyclin T / deficiency
  • Cyclin T / genetics*
  • Cyclin-Dependent Kinase 9 / deficiency
  • Cyclin-Dependent Kinase 9 / genetics*
  • Gene Expression Regulation, Developmental*
  • Genes, myc*
  • Isoxazoles / pharmacology
  • Leflunomide
  • Morpholinos / pharmacology
  • Neural Crest / embryology*
  • Positive Transcriptional Elongation Factor B / deficiency
  • Positive Transcriptional Elongation Factor B / genetics*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • RNA Polymerase II / metabolism
  • SOXE Transcription Factors / biosynthesis
  • SOXE Transcription Factors / genetics
  • Transcription Elongation, Genetic* / drug effects
  • Transcription, Genetic
  • Xenopus Proteins / deficiency
  • Xenopus Proteins / genetics*
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics

Substances

  • Cyclin T
  • Isoxazoles
  • Morpholinos
  • Proto-Oncogene Proteins c-myc
  • SOXE Transcription Factors
  • Xenopus Proteins
  • Positive Transcriptional Elongation Factor B
  • Cyclin-Dependent Kinase 9
  • RNA Polymerase II
  • Leflunomide