期刊
DEVELOPMENT
卷 146, 期 24, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.180133
关键词
Paf1 complex; Neural crest; Stem cells; Transcription pausing; Zebrafish mutant; P-TEFb
资金
- National Institutes of Health (NIH) [1P01HD048886, 1R01HD081950]
- Melanoma Research Alliance
- NIH [PO1 CA163222, UM1 HL098160]
- Huntsman Cancer Foundation
- Nuclear Control of Cell Growth and Differentiation Program at the Huntsman Cancer Institute
- National Cancer Institute/National Institutes of Health [P30CA042014]
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 nearidentical NC phenotypes; alyron mutant embryos carrying a null mutation in pail were analyzed in detail. In the absence of zygotic pail 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.
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