NEURONAL DEFECTS AND DELAYED WOUND-HEALING IN MICE LACKING FIBROBLASTGROWTH-FACTOR-2

Basic fibroblast growth factor (FGF2) is a wide-spectrum mitogenic, an giogenic, and neurotrophic factor that is expressed at low Bevels in m any tissues and cell types and reaches high concentrations in brain an d pituitary, FGF2 has been implicated in a multitude of physiological and pathological processes, including limb development, angiogenesis, wound healing, and tumor growth, but its physiological role is still u nclear, To determine the function of FGF2 in vivo, we have generated F GF2 knockout mice, lacking ail three FGF2 isoforms, by homologous reco mbination ire embryonic stem cells. FGF2(-/-) mice are viable, fertile and phenotypically indistinguishable from FGF2(+/+) littermates by gr oss examination, However, abnormalities ire the cytoarchitecture of th e neocortex, most pronounced in the frontal motor-sensory area, can be detected by histological and immunohistochemical methods. A significa nt reduction in neuronal density is observed in most layers of the mot or cortex in the FGF2(-/-) mice, with layer V being the most affected, Cell density is normal in other regions of the brain such as the stri atum and the hippocampus. In addition, the healing of excisional skin wounds is delayed in mice lacking FGF2. These results indicate that FG F2, although not essential for embryonic development, plays a specific role in cortical neurogenesis and skin wound healing in mice, which, in spite of the apparent redundancy of FGF signaling, cannot be carrie d out by other FGF family members.