FGF2 modulates simultaneously the mode, the rate of division and the growth fraction in cultures of Radial Glia

Abstract

ABSTRACTRadial Glial progenitors in the mammalian developing neocortex have been shown to follow a deterministic differentiation program restricted to an asymmetric-only mode of division. This feature seems incompatible with their well known ability to expand in number when cultured in vitro, driven by Fibroblast Growth Factor 2 and other mitogenic signals. The changes in their differentiation dynamics that allow this transition from in vivo asymmetric-only division mode to an in vitro self-renewing culture have not been fully characterized. Here we combine experiments of Radial Glia cultures with theory and numerical models to show that Fibroblast Growth Factor 2 has a triple effect by simultaneously increasing the growth fraction, promoting symmetric divisions and shortening the length of the cell cycle. This combined effect of Fibroblast Growth Factor 2 in the differentiation dynamics of Radial Glial progenitors partner to establish and sustain a pool of rapidly proliferating in vitro pool of Radial Glial progenitors.