Cellular and molecular regulation of heart development
The work in our laboratory has focused on the commitment, differentiation and function of cardiac and vascular cells in the embryo. The early heart development and vasculogenesis provide excellent systems to examine fundamental issues in developmental biology. Heart development involves the commitment of embryogenic cells to the cardiogenic mesodermal lineage, coordinated activation of cell-specific genes in committed cells, and the diversification of progenitors in a highly patterned manner leading to the generation of distinct myogenic phenotypes.
Our current work is focused on the function of two genes that were discovered in our laboratory and analysis of the conserved system whereby coelomates generate vessels to organs during development.
LEK1 is a large and complex protein that regulates proliferation and differentiation of cardiac myocytes.
Through a series of biochemical, morphological, genetic and cell biological experiments, we have determined that LEK1 proteins function in cell movement, trafficking and division through its interaction with Rb proteins, the cytoskeleton and the SNARE complex. Our ongoing work is focused on conditionally inhibiting the function of this gene in developing mice and continuing our studies of LEK1 interaction with subcellular domains.
Bves is an integral membrane protein discovered by former members of the lab. This protein is essential for proper cell/cell interaction during coronary vessel development. Our work has shown that Bves is one of the first proteins trafficked to points of cell/cell contact and that it associates with cytoplasmic proteins that regulate cell/cell adhesion, process formation and movement. Our goal is to determine how disruption of Bves function impacts embryonic development in vertebrate and invertebrate development.
Lastly, we have determined that blood vessel formation to internal organs has a conserved program that is been overlooked heretofore. We have discovered that vasculogenesis to the heart and gut is linked to the formation of the embryonic coelom and that progenitors of these blood vessels arise via a mechanism unlike that of the body wall and limbs. We are now disrupting this developmental system in an effort to understand the cellular and molecular mechanisms driving this process.