FGF2 modulates simultaneously the mode, the rate of division and the growth fraction in cultures of radial glia

Abstract

ABSTRACT Radial 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 increase 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 numerical models and a branching process theoretical formalism 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. These combined effects partner to establish and sustain a pool of rapidly proliferating radial glial progenitors in vitro. We also show that, in conditions of variable proliferation dynamics, the branching process tool outperforms other commonly used methods based on thymidine analogs, such as BrdU and EdU, in terms of accuracy and reliability.