Fibroblast Growth Factor Receptor Signaling in Brain Development

Yale University, New Haven CT

Investigators

Abstract

0083104 Vaccarino Fibroblast Growth Factors (FGF) are thought to increase the generation of neurons in the Central Nervous System. These factors elicit their effect by binding to FGF receptors on the surface of neural progenitor cells. The function of each of the four existing FGF receptors during normal brain development is unclear. This Project investigates whether FGF receptor 1 (FGFR-1) controls the growth of the mammalian brain. To study the function of FGFR-1 in brain development, mice will be generated that lack the FGFR-1 gene only in the brain. These mice are produced by targeting a DNA recombinase called Cre to cells of the developing brain. The Cre recombinase will excise critical segments of the FGFR-1 gene in these cells. The resulting brain-specific FGFR-1 mutants will be studied to elucidate the role of FGFR-1 in cell proliferation and fate. Cognitive functions strongly correlate with an increase in the relative size and complexity of the brain. Studying the basic mechanisms that construct the brain during early development may shed light on the underlying basis for cognitive functions. In addition, because neural progenitor cells persist in the adult mammalian brain and may continue to use FGF-regulated mechanisms, this research may help understand the role of this receptor in brain cell renewal and repair.