Neural crest cell-autonomous functions of fibronectin in cardiovascular development
Optical projection tomography and 3D reconstruction of the entire heart and the aortic arch arteries
We discovered that fibronectin specifically synthesized by the neural crest plays a requisite role in the regulation of mammalian cardiovascular development and morphogenesis of the aortic arch arteries. In particular, we found that neural crest-synthesized fibronectin facilitates Notch signaling and the differentiation of neural crest cells into vascular smooth muscle cells around pharyngeal arch arteries. Current studies in the lab are focused on understanding the mechanisms of this regulation.
Roles of fibronectin & integrin a5 in the formation of the pharyngeal arch arteries
We found that the expression of fibronectin and integrin a5 in pharyngeal mesoderm, endoderm and surface ectoderm regulates the formation of the pharyngeal arch arteries. We are using temporal lineage mapping analysis, whole-mount immunofluorescence and 3D imaging to understand the mechanisms, whereby cell-extracellular interactions regulate blood vessel morphogenesis.
Stage-dependent development of the pharyngeal arch arteries. Blood vessels (blue) are imaged with the help of confocal immunofluorescence microscopy in whole embryos using antibody to Pecam1. Vasculature in the 4th arch is highlighted using surface rendering. Vascular plexus is rendered in pink, while the pharyngeal arch artery is rendered in green. The scale bar is 100 μm
Mechanisms regulating the formation of the pharyngeal arch arteries from endothelial progenitors
Studies under this project will identify progenitors that give rise to the endothelium of the pharyngeal arch arteries, and the pathways regulating arch artery development. This will help us understand mechanisms and etiology of congenital heart disease, including DiGeorge syndrome, caused by the most common chromosomal abnormality in humans.