FGF2 CONCENTRATION REGULATES THE GENERATION OF NEURONS AND GLIA FROM MULTIPOTENT CORTICAL STEM-CELLS

The embryonic cerebral cortex contains a population of stem-like found er cells capable of generating large, mixed clones of neurons and glia in vitro. We report that the default state of early cortical stem cel ls is neuronal, and that stem cells are heterogeneous in the number of neurons that they generate. In low fibroblast growth factor (FGF2) co ncentrations, most maintain this specification, generating solely neur onal progeny. Oligodendroglial production within these clones is stimu lated by a higher, threshold level of FGF2, and astrocyte production r equires additional environmental factors. Because most cortical neuron s are born before glia in vivo, these data support a model in which th e scheduled production of cortical cells involves an intrinsic neurona l program in the early stem cells and exposure to environmental, glia- inducing signals.