"An Introduction to Our Lab" -Victoria Bautch
The research in my lab centers on the molecules and processes that control development in the mouse. Our major focus is the study of how blood vessels form and are patterned during mouse development.  The group of scientists working in my lab include graduate students, post-docs, research technicians, and undergraduates. Click here to see current lab members; click here to see past members of the lab.
 

The process of blood vessel formation is crucial to vertebrate development, because embryos cannot develop without a source of oxygen and nutrients. Thus, blood vessels begin to form very early in mouse development, along with the heart and primitive blood cells. Pictured here is a mouse embryo, halfway through development, with all the blood vessels visible. Blood vessel formation is also very important in several common diseases-- for example, the occlusion of blood vessels that characterize heart disease is likely to cause a fatal heart attack unless new blood vessels can be formed quickly to nourish the affected heart. Conversely, the blood vessels that form to nourish a small tumor can help the tumor grow and eventually metastasize. Therefore, blocking the formation of tumor blood vessels could provide important cancer therapy.

We have taken two approaches to study blood vessel formation during development. To understand the basic differentiation signals, we utilize an in vitro system in which primitive blood vessels form in a tissue culture dish. We use mouse embryonic stem cells that are undifferentiated but can differentiate to provide every cell type of the mouse. When differentiated in cultures, the cells reproducibly differentiate into a subset of cells, including endothelial cells that are the basic building blocks of all blood vessels. These endothelial cells organize into primitive vessels in culture. Thus, we have easy access to important stages of early blood vessel formation that usually occur in the mother's body. We have obtained several cell lines that have mutations in genes that are important in blood vessel formation because they disrupt a specific signaling pathway. Click here to see how a mutation in the flt receptor (part of the vascular endothelial growth factor pathway) affects the growth of blood vessels.  We can now use this system to watch blood vessels develop in real time...check out some of our movies! For more details on some current projects utilizing this model, click here.

A complementary approach is to study the process of blood vessel formation in vivo. We analyze mouse embryos to verify that conclusions formed from the culture model are valid in vivo. We also study aspects of vascular pattern formation in vivo. One aspect of this work utilizes mouse-quail chimeras, to determine where vascular precursor cells are found in the mouse, and how mouse cells respond in the quail host environment to form vessels. We can then use mice that have mutations in genes that are important in blood vessel formation. Pictured here is a quail embryo at 72 hours after having mouse tissue grafted into the quail. Specifically, presomitic mesoderm on one side of the quail was removed and replaced with the same tissue from the mouse embryo. Small blood vessels are seen developing from the mouse tissue which is "marked" blue. To find out more about projects that address questions of vascular patterning, click here.

Recently we have investigated a signaling pathway that we believe is involved in the vascular complications of diabetes. We found a novel receptor for this pathway using a gene trap screen, and we deleted this receptor in embryonic stem cells and in mice. We are now testing the effects of loss of this gene in diabetic mouse models, to determine if mice missing the gene are protected from diabetic problems. We also are investigating the role of this pathway in the fetal birth defects that occur with higher frequency in diabetic mothers. To learn more about projects that address signaling in diabetes, click here.

(updated 8/15/05).

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