Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification

Abstract

The paired pharyngeal arch arteries (PAAs) are transient blood vessels connecting the heart with the dorsal aorta during embryogenesis. Although PAA malformations often occur along with pharyngeal pouch defects, the functional interaction between these adjacent tissues remains largely unclear. Here we report that the ablation of pouches in zebrafish embryos impairs PAA progenitor specification and leads to the absence of PAA structures. Through time-lapse imaging studies, we reveal that the segmentation of pharyngeal pouches coincides spatiotemporally with the emergence of PAA progenitor clusters. These pouches physically associate with pharyngeal mesoderm in discrete regions and provide a niche microenvironment for PAA progenitor commitment by expressing BMP proteins. Specifically, tissue specific knockdown experiments demonstrate that pouch-derived BMP2a and BMP5 are the primary niche cues responsible for activating the BMP/Smad pathway in pharyngeal mesoderm, thereby promoting progenitor specification. In addition, BMP2a and BMP5 play a primary inductive function in the expression of the cloche gene npas4l in PAA progenitors. Mutation of the cloche locus represses the specification of PAA progenitors and generates ectopic muscle precursors in the pharyngeal mesoderm. Therefore, our results support a critical role of pharyngeal pouches in establishing a progenitor niche for PAA morphogenesis via BMP2a/5 expression.