REGULATION OF NEURAL PRECURSOR DIFFERENTIATION IN THE EMBRYONIC AND ADULT FOREBRAIN

1. Precursors form the neuroepithelium of the developing cortex and also from the adult sub‐ventricular zone, can be cloned in vitro after stimulation with fibroblast growth factor (FGF)‐2 and have the potential to give rise to both neurons and glia. The generation of neurons from these clones can be stimulated by either a factor derived from an astrocyte‐precursor line, Ast‐1, or FGF‐1. 2. Neuronal differentiation stimulated by FGF‐1 can be inhibited by diacylglycerol‐lipase inhibitor and mimicked by arachidonic acid, suggesting that the neuronal differentiation is signalled through the PCLγ pathway. 3. The sequential expression of FGF‐2 and FGF‐1 within the developing forebrain neuroepithelium fits with the different functions the two FGF play in precursor regulation. 4. We have shown that the precursor response to FGF‐1 is regulated by a heparan sulphate proteoglycan (HSPG) expressed within the developing neuroepithelium. Precursors restricted to the astrocyte cell lineage can be stimulated by epidermal growth factor or FGF‐2; however, the differentiation into GFAP positive astrocytes appears to require a cytokine acting through the leukaemia inhibitory factor β receptor.