Basic Fibroblast Growth Factor (Fgf2) Is Necessary for Cell Proliferation and Neurogenesis in the Developing Cerebral Cortex

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.

Expansion, folding, and abnormal lamination of the chick optic tectum after intraventricular injections of FGF2

“…Specifically, intraventricular injections of FGF2 in embryonic rats and mice increases neocortical neuron numbers (13,29), as one would expect if FGF2 prolongs precursor proliferation. Several studies suggest that proliferation rate and neuronal migration are relatively unaffected by FGF2 manipulations in vivo (13,(29)(30)(31), although in vitro studies have reported more complex effects (32).…”

Essential role of Shp2-binding sites on FRS2α for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells

“…It was reported that FGF2 Ϫ/Ϫ mice had mild defects in proliferation of neural stem cells at early stages (38,40 4A). In addition, ERK activation in mutant brains was higher at E14.5 than at E11.5 (Fig.…”

Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation

“…Third, during the early phase of development, neural progenitor cells proliferate in response to bFGF during the Cell Research | www.cell-research.com VEGF and bFGF regulate NSC proliferation 74 npg neurogenic phase [24,25]. It has been reported that knocking out bFGF during critical periods of brain development led to an overall reduction in progenitor proliferation and subsequent neuronal differentiation [26,27].…”