Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation.

摘要: Vertebrate heart development requires the integration of temporally distinct differentiating progenitors. However, few signals are understood that restrict size later-differentiating outflow tract (OFT). We show improper specification and proliferation second field (SHF) progenitors in zebrafish lazarus (lzr) mutants, which lack transcription factor Pbx4, produces enlarged hearts owing to an increase ventricular smooth muscle cells. Specifically, Pbx4 initially promotes partitioning SHF into anterior progenitors, contribute OFT, adjacent endothelial cell posterior pharyngeal arches. Subsequently, limits progenitor (SHFP) proliferation. Single RNA sequencing nkx2.5+ cells revealed previously unappreciated differentiation states subpopulations normally reside within arterial pole heart. transcriptional profiles Pbx4-deficient SHFPs less display characteristics discrete proliferative anterior, differentiated cardiomyocyte populations. Therefore, our data indicate generation proper OFT arch arteries Pbx-dependent stratification unique facilitate both homeotic-like transformations limit production SHF.