Pharyngeal Arch Artery Development
In higher vertebrates, the aorta and it's branches derive critical segments from transient pairs of embryonic vessels termed pharyngeal arch arteries (PAAs) that undergo extensive remodeling to produce the asymmetric pattern present at birth. Unlike mammals, the zebrafish PAAs are NOT remodeled, but instead mature into the gill circulation.
Despite the ultimate differences in PAA function, the early anatomic configurations of the PAAs are virtually indistinguishable between zebrafish and humans , suggesting that the biological determinants of PAA establishment are highly conserved.With unmatched real-time imaging coupled with embryonic and genetic accessibility, the zebrafish is an ideal model organism to discover the cellular and molecular mechanisms that govern PAA formation, an understudied yet vital research area with the capacity to change how we diagnose and treat newborn great vessel malformations.
The following projects are currently underway or available to pursue in our laboratory:
Pathways Regulating PAA Development: From an unbiased small molecule screen in zebrafish embryos, we have isolated compounds that disrupt PAA formation. We are interested in understanding mechanistically how each compound blocks PAA development.
Modeling Great Vessel CHDs: We are generating and characterizing zebrafish mutants in CHD loci that have been reported to segregate with great vessel malformations.
Progenitor Heterogeneity: We reported that nkx2.5-expressing cells localized in anterior lateral plate mesoderm are the source of ventricular cardiomyocytes, three outflow tract lineages, facial muscles, and PAA endothelium. We are interested in unravelling the heterogeneity within the nkx2.5-expressing population.