Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex

Little is known about regionally specific signals that control the number o f neuronal progenitor cells in vivo. We have previously shown that the germ line mutation of the basic fibroblast growth factor (Fgf2) gene results in a reduction in the number of cortical neurons in the adult. We show here th at Fgf2 is expressed in the pseudostratified ventricular epithelium (PVE) i n a dorsoventral gradient and that Fgf2 and its receptor, Fgfr-1, are downr egulated by mid to late stages of neurogenesis. In Fgf2 knockout mice, the volume and cell number of the dorsal PVE (the cerebral cortical anlage) are substantially smaller, whereas the volume of the basal PVE is unchanged. T he dorsal PVE of Fgf2 knockout mice has a 50% decrease in founder cells and a reduced expansion of the progenitor pool over the first portion of neuro genesis. Despite this reduction, the degree of apoptosis within the PVE is not changed in the Fgf2 knockouts. Cortical neuron number was decreased by 45% in Fgf2 knock-out mice by the end of neurogenesis, whereas the number o f neurons in the basal ganglia was unaffected. Microscopically, the frontal cerebral cortex of neonatal Fgf2 null mutant mice lacked large neurons in deep cortical layers. We suggest that Fgf2 is required for the generation o f a specific class of cortical neurons arising from the dorsal PVE.