This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. New blood vessel growth or neovascularization, can be categorized into vasculogenesis and angiogenesis. Vasculogenesis is de novo formation of blood vessels from endothelial progenitor cells (EPS) which differentiate in situ, spread, migrate and coalesce to give rise to a capillary network. In contrast, angiogenesis results from the sprouting of pre-existing endothelial cells. Cell migration, assembly into cords-like structures, formation of vascular lumens and organization into capillary networks are essential steps in the vasculogenic process which are poorly understood. It has been speculated that the development of beiomechanical tension between cells drives the reorganization of cells into cords and capillary like structures. Nonmuscle myosin II is the molecular motor responsible for generation of cellular tension;however, myosin II's role in capillary formation is unknown.
The aim of the proposed research is to define the role of myosin II in vascular morphogenesis. The primary hypothesis underlying the proposed work dictates that myosin II is essential for vascular development. This hypothesis states that activation of myosin II resulting in generation of cellular tension is an absolute requirement for formation of capillary networks. The objectives of this application are: 1) to characterize pulmonary capillary morphogenesis;2) determine the role of nonmuscle myosin II (myosin IIA and IIB) during pulmonary capillary formation and 3) to identify the signaling pathways which activate myosin II at specific stages of capillary formation. Functionally, regulated phosphorylation of myosin II would allow developing capillary networks to react to a variety of physiological signals with graded contractile responses and tension generation.
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