Mervin C. Yoder, Jr., M.D. Associate Professor of Biochemistry and Microbiology Associate Professor of Pediatrics Indiana University School of Medicine

Background
Professor, Departments of Pediatrics and of Biochemistry and Molecular Biology
Neonatology Fellowship, University of Pennsylvania, Philadelphia, PA
Residency, Children's Hospital of Philadelphia, Philadelphia, PA
M.D., Indiana University School of Medicine, 1980

Research

The first mammalian blood cells appear in the extraembryonic yolk sac early in development. While both blood and endothelial cells are derived from extraembryonic mesoderm, we know little of the cellular interactions that are required to construct the first vascular structures called blood islands. Our recent evidence suggests that the first blood cells that emerge in the yolk sac migrate into and proliferate withn the yolk sac between the visceral endoderm and underlying uncommitted mesoderm cells. The endothelial precursors, angioblasts, migrate between the visceral endoderm and overly the developing blood cells. On embryonic day 8, the angioblasts penetrate through the blood band to circumscribe the blood cells and form intact blood islands. Soon after, a new population of cells emerges from the endothelial lining of the blood islands representing the definitive hematopoietic progenitor cell population. Thus, both primitive erythroid cells and definitive progenitor cells are circulating toward the embryo at the time of onset of the first cardiac contractions.

We are determining the role of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (Flk-1) in the process of primitive erythroid progenitor (EryP) cell migration and proliferation in the murine yolk sac. Using a variety of VEGF and Flk-1 deficient mutant mice and in vitro manipulation of cultured whole embryos, we are able to examine the direct roles of these molecules on EryP function. We are also able to isolate and culture primary and embryonic stem (ES) cell-derived EryP using a strategy recently published from our laboratory. We are also examining the role of several transcription factors in the emergence and maintenance of the definitive progenitor cell population in the late yolk sac using genetic approaches in mutant mice.

More Information:
Herman B Wells Center for Pediatric Research