Identification of two distinct types of multipotent neural precursors that appear sequentially during CNS development.

Epidermal growth factor (EGF) and fibroblast growth factor (FGF)-2 control neural stem cell proliferation in vitro and the formation of neurospheres. Neurospheres contain precursors that respond to both EGF and FGF-2 (E/F cells). E/F cells appear to originate from cells that initially respond to FGF-2 only but undergo a transition in growth factor responsiveness during in vitro culturing. It is unclear whether a similar change in growth factor responsiveness of multipotent precursors takes place in vivo and how this may affect neural precursor properties. Here I provide evidence that FGF-2-responsive precursors and E/F cells appear sequentially during CNS development. This transition from the early precursors (FGF-2-responsive cells) to the late precursors (E/F cells) takes place between E14 and E18. The two types of precursors are morphologically and antigenically distinct. E/F cells are very large and show strong nestin immunoreactivity. Thus the putative neurosphere-forming E/F cells are present in vivo and their generation is developmentally programmed. Their unique morphology may provide a basis for their isolation.