Research Interests: Molecular mechanisms of cell fate specification during blood vessel development and organogenesis
During early development, the embryo acquires its shape and complexity of tissues via the coordination of fundamental cellular processes, such as cell signaling, cell migration, cell adhesion and cell differentiation. During this amazing process, a multitude of different signals must be exchanged between cells at precise times and locations, often in a step-wise manner. Our lab is interested in understanding the molecular mechanisms that underlie organogenesis in the embryo, using the model organisms mouse and frog.
More specifically, the focus of our research is the developing vascular endothelium. We want to answer the questions: how do tissues direct blood vessel patterning via angiogenic factors and, how does the endothelium, in turn, influence embryonic cell differentiation? Our hypothesis is that reciprocal signals underlie the coordinated growth of blood vessels and morphogenesis of organs, and that mutual signaling forms the basis for interdependent physiological relationships that last into adulthood. Understanding this endothelium-tissue crosstalk will be the focus of our research.
Recently, we have demonstrated a developmental role for endothelium in the induction/maintenance of pancreatic beta cells, while another group has identified its influence on hepatic cells. The gene products and signaling molecules mediating these effects, however, have not been identified. Elucidating the nature of endothelial signals during development will help uncover the role blood vessels play in organogenesis, tumorigenesis, tissue maintenance and perhaps stem cell differentiation.
By using the mouse and the frog as model systems, we are able to combine genetics, molecular manipulations, in vitro culture techniques and classical embryology to investigate cell differentiation, patterning and key signaling molecules in development. Using these techniques, we hope to build a comprehensive picture of the fundamental mechanisms that underlie the coordinated growth and interdependence of blood vessels and organs. Understanding these principles will help us to identify and characterize molecular lesions that underlie human birth defects and disease.
RESEARCH INTERESTS
Developmental biology
Organogenesis
Angiogenesis/vasculogenesis
Stem cell differentiation
RECENT PUBLICATIONS
Lammert, E.*, Cleaver, O.* and Melton, D., "Induction of pancreatic differentiation by signals from blood vessels." Science, 294:564-567, 2001
Cleaver, O. and Krieg, P.A., "Notochord patterning of the endoderm." Dev Biol, 234:1-12, 2001
Sherwood RI, Jitianu C, Cleaver O, Shaywitz DA, Lamenzo JO, Chen AE, Golub TR, Melton DA., "Prospective Isolation and Global Gene Expression Analysis of Definitive and Visceral Endoderm." Dev. Biol., 304:541-555, 2007
Soukup C. Levenberg S. and Cleaver O., "In vitro differentiation of endothelial cells from human embryonic stem cells." Human Embryonic Stem Cells: A Practical Approach., John Wiley & Sons.:229-248, 2007
Cleaver, O. and Melton, D.A., "Endothelial signaling during development." Nature Medicine, 9:661-668, 2003
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