PDGF signaling from pharyngeal pouches promotes arch artery morphogenesis

The great vessels of the heart originate from the pharyngeal arch arteries (PAAs). Anomalies of the PAAs often occur together with pharyngeal pouch malformations, but the reasons for this phenomenon are not fully understood. In the current study, we show that platelet-derived growth factor (PDGF) signaling derived from the pharyngeal pouches plays an important function in PAA vasculogenesis. During PAA development in zebrafish embryos, pdgfαa and pdgfαb are expressed in the developing pharyngeal pouches. Results from loss-of-function experiments revealed a critical role of these genes in PAA formation. We found that nitroreductase (NTR)-mediated pouch ablation distinctly decreased PDGF receptor tyrosine phosphorylation, yielding a severe loss of PAAs. Importantly, pouch-specific overexpression of pdgfαa in pdgfαa^-/-; pdgfαb^-/- mutants significantly relieved the PAA defects, which indicated a primary role of pharyngeal pouch-expressed PDGF ligands in signal activation and PAA morphogenesis. Our findings further showed that PDGF signaling was indispensable for the proliferation of PAA angioblasts. Together, these results established a role for PDGFαa- and PDGFαb-mediated tissue-tissue interaction during PAA development.