ABSTRACT
Little is known about regionally specific signals that control the number of neuronal progenitor cells in vivo. We have previously shown that the germline 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 that Fgf2 is expressed in the pseudostratified ventricular epithelium (PVE) in a dorsoventral gradient and that Fgf2 and its receptor, Fgfr-1, are downregulated 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. The 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 neurogenesis. 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 knockout mice by the end of neurogenesis, whereas the number of 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 of a specific class of cortical neurons arising from the dorsal PVE.
Subject(s)
Cerebral Cortex/embryology , Fibroblast Growth Factor 2/physiology , Gene Expression Regulation, Developmental , Receptor Protein-Tyrosine Kinases/physiology , Receptors, Fibroblast Growth Factor/physiology , Telencephalon/embryology , Animals , Apoptosis , Cell Division , Choroid Plexus/embryology , Embryonic and Fetal Development , Fibroblast Growth Factor 2/deficiency , Fibroblast Growth Factor 2/genetics , Germ-Line Mutation , Gestational Age , Mice , Mice, Knockout , Prosencephalon/embryology , Receptor Protein-Tyrosine Kinases/genetics , Receptor, Fibroblast Growth Factor, Type 1 , Receptors, Fibroblast Growth Factor/geneticsABSTRACT
The fibroblast growth factor (FGF) family comprises several members with distinct patterns of expression in the developing central nervous system. FGFs regulate the early specification and the subsequent growth of central nervous system regions. These different actions require the coordinated activation of distinct sets of target genes by FGFs at the appropriate stage of development. The role of FGF2 in the growth and morphogenesis of the cerebral cortex is reviewed in detail. The cellular and molecular mechanisms that underlie the action of FGF2 on cortical development are discussed.
