@article{e23cd58cb3844ea9b8bc377a4dae43fd,
title = "The Paf1 complex and P-TEFb have reciprocal and antagonist roles in maintaining multipotent neural crest progenitors",
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.",
keywords = "Neural crest, P-TEFb, Paf1 complex, Stem cells, Transcription pausing, Zebrafish mutant",
author = "Jurynec, {Michael J.} and Xiaoying Bai and Bisgrove, {Brent W.} and Haley Jackson and Alex Nechiporuk and Palu, {Rebecca A.S.} and Grunwald, {Hannah A.} and Su, {Yi Chu} and Kazuyuki Hoshijima and {Joseph Yost}, H. and Zon, {Leonard I.} and Grunwald, {David Jonah}",
note = "Funding Information: This work is dedicated to our friend Chris J. Cretekos (1966-2014), who had the insight to generate and characterize the alyronz12 mutant. Rob Cornell generously provided tfap2a/c MO-depleted embryos for analysis and Bruce Appel generously provided the Sox10 antibody. We thank our colleagues Chi-Bin Chien, Rich Dorsky and Rod Stewart for scientific guidance and critical feedback. We thank the University of Utah Health Sciences Core Facilities for DNA sequencing, oligonucleotide synthesis, imaging support and zebrafish husbandry. This work was supported by grants to D.J.G. from the National Institutes of Health (NIH) (1P01HD048886 and 1R01HD081950); to L.I.Z. from the Melanoma Research Alliance and the NIH (PO1 CA163222); and to H.J.Y. from the NIH (UM1 HL098160). We acknowledge direct financial support for the research reported in this publication from the Huntsman Cancer Foundation and the Nuclear Control of Cell Growth and Differentiation Program at the Huntsman Cancer Institute. We also acknowledge support from the National Cancer Institute/National Institutes of Health (P30CA042014). Deposited in PMC for release after 12 months. Funding Information: This work was supported by grants to D.J.G. from the National Institutes of Health (NIH) (1P01HD048886 and 1R01HD081950); to L.I.Z. from the Melanoma Research Alliance and the NIH (PO1 CA163222); and to H.J.Y. from the NIH (UM1 HL098160). We acknowledge direct financial support for the research reported in this publication from the Huntsman Cancer Foundation and the Nuclear Control of Cell Growth and Differentiation Program at the Huntsman Cancer Institute. We also acknowledge support from the National Cancer Institute/National Institutes of Health (P30CA042014). Deposited in PMC for release after 12 months. Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd",
year = "2019",
doi = "10.1242/dev.180133",
language = "English (US)",
volume = "146",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "24",
}