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

Michael J. Jurynec, Xiaoying Bai, Brent W. Bisgrove, Haley Jackson, Alex Nechiporuk, Rebecca A.S. Palu, Hannah A. Grunwald, Yi Chu Su, Kazuyuki Hoshijima, H. Joseph Yost, Leonard I. Zon, David Jonah Grunwald

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberdev180133
JournalDevelopment (Cambridge)
Volume146
Issue number24
DOIs
StatePublished - 2019

Keywords

  • Neural crest
  • P-TEFb
  • Paf1 complex
  • Stem cells
  • Transcription pausing
  • Zebrafish mutant

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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