alyron (aln) zygotic mutant zebrafish lack neural crest (NC)-derived tissues, such as melanophores, dorsal root ganglia and enteric neurons. David Grunwald, Mick Jurynec and colleagues demonstrate that this NC phenotype is due to loss of RNA polymerase-associated factor 1 complex (Paf1C) function. The researchers show that paf1 is required cell autonomously to maintain the NC lineage: without zygotic paf1 the NC lineage fails to maintain NC gene expression and populate its target destinations in the embryo. Additional tissue progenitors, such as erythroid progenitors, are similarly affected in the mutant. Paf1C has multiple roles in modulating transcription elongation. To identify the particular Paf1C function required for maintenance of NC progenitors, the authors interrogate functions of complexes known to interact with Paf1C. The authors find that loss of Cdk9 (a subunit of the pause release factor P-TEFb) suppresses the NC development defects of aln mutants. Not only do aln;cdk9 double mutants generate melanophores, the cdk9 single mutants have expanded populations of NC progenitors and their descendants, which indicates that delaying transcription elongation is important for maintenance of NC progenitors. Together, these data indicate that the antagonistic activity of Paf1C and P-TEFb during transcription is required for the maintenance of NC progenitors in vivo.
