The Paf1 complex and P-TEFb have reciprocal and antagonist roles in maintaining multipotent neural crest progenitors

Development. 2019 Dec 16;146(24):dev180133. doi: 10.1242/dev.180133.


Multipotent progenitor populations are necessary for generating diverse tissue types during embryogenesis. We show the RNA polymerase-associated factor 1 complex (Paf1C) is required to maintain multipotent progenitors of the neural crest (NC) lineage in zebrafish. Mutations affecting each Paf1C component result in near-identical NC phenotypes; alyron mutant embryos carrying a null mutation in paf1 were analyzed in detail. In the absence of zygotic paf1 function, definitive premigratory NC progenitors arise but fail to maintain expression of the sox10 specification gene. The mutant NC progenitors migrate aberrantly and fail to differentiate appropriately. Blood and germ cell progenitor development is affected similarly. Development of mutant NC could be rescued by additional loss of positive transcription elongation factor b (P-TEFb) activity, a key factor in promoting transcription elongation. Consistent with the interpretation that inhibiting/delaying expression of some genes is essential for maintaining progenitors, mutant embryos lacking the CDK9 kinase component of P-TEFb exhibit a surfeit of NC progenitors and their derivatives. We propose Paf1C and P-TEFb act antagonistically to regulate the timing of the expression of genes needed for NC development.

Keywords: Neural crest; P-TEFb; Paf1 complex; Stem cells; Transcription pausing; Zebrafish mutant.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Cell Lineage / genetics*
  • Cyclin-Dependent Kinase 9 / genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / physiology*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / physiology
  • Neural Crest / cytology*
  • Neural Crest / physiology
  • Neural Stem Cells / cytology
  • Neural Stem Cells / physiology*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Positive Transcriptional Elongation Factor B / antagonists & inhibitors
  • Positive Transcriptional Elongation Factor B / metabolism
  • Positive Transcriptional Elongation Factor B / physiology*
  • RNA Polymerase II / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*


  • Multiprotein Complexes
  • Nuclear Proteins
  • Transcription Factors
  • Zebrafish Proteins
  • paf1 protein, zebrafish
  • Positive Transcriptional Elongation Factor B
  • Cyclin-Dependent Kinase 9
  • RNA Polymerase II