Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon

Multipotent, self-renewing neural stem cells reside in the embryonic mouse telencephalic germinal zone. Using an in vitro neurosphere assay for neural stem cell proliferation, we demonstrate that FGF-responsive neural stem ce lls are present as early as E8.5 in the anterior neural plate, but EGF-resp onsive neural stem cells emerge later in development in a temporally and sp atially specific manner. By separately blocking EGF and FGF2 signaling, we also show that EGF alone and FGF2 alone can independently elicit neural ste m cell proliferation and at relatively high cell densities separate cell no nautonomous effects can substantially enhance the mitogen-induced prolifera tion. At lower cell densities, neural stem cell proliferation is additive i n the presence of EGF and FGF2 combined, revealing two different stem cell populations. However both FGF-responsive and EGF-responsive neural stem cel ls retain their self-renewal and multilineage potential, regardless of grow th factor conditions. These results support a model in which separate, line age-related EGF- and FGF-responsive neural stem cells are present in the em bryonic telencephalic germinal zone, (C) 1999 Academic Press.