Sealing a cell's fate

A collaboration of scientists, led by Dr. Janet Rossant at the University of Toronto and The Samuel Lunenfeld Research Institute at Mount Sinai Hospital, has identified two genes whose combined expression drives the development of the blood and blood vessels in early embryogenesis. This discovery lends new insight into the molecular cues that direct blood and vascular development -- a crucial event in both normal and pathological processes, like tumor angiogenesis.

Dr. Rossant and colleagues have discovered that the proteins encoded by two genes, called Flk1 and Tal1, coax embryonic progenitor cells to become either cells that compose the blood (hematopoietic cells), line the blood vessels (endothelial cells), or help support the blood vessel walls (smooth muscle cells). While it has been hypothesized that endothelial and hematopoietic cells are derived from a common progenitor cell, called the hemangioblast, Dr. Rossant and colleagues now show that the co-expression of Flk1 and Tal1 in the hemangioblast is necessary for normal endothelial, hematopoietic, and smooth muscle cell specification.

"We are interested in trying to understand the relationships between cells of the blood, and the cells lining the blood vessels in which they are transported. Surprisingly, our studies and those of others suggest that, at least in the early embryo, these two cells come from a common progenitor, the hemangioblast. What is more, the same progenitor can give rise to the smooth muscle cells of the vessel walls," explains Dr. Rossant

Flk1 encodes a cell surface receptor for the vascular endothelial growth factor (VEGF), a crucial factor in angiogenesis. Transgenic mice lacking Flk1 fail to form endothelial and hematopoietic cells, and also fail to express the transcription factor Tal1. To test the effect of Tal1 on hemangioblast development, Dr. Rossant and colleagues reintroduced Tal1 into Flk1-deficient mouse embryos and embryonic stem (ES) cells.


Contact: Heather Cosel
Cold Spring Harbor Laboratory

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