MULTIPLE ROUTES TO ASTROCYTIC DIFFERENTIATION IN THE CNS

Ciliary neurotrophic factor (CNTF) acts instructively to switch multip otent stem cells ct the CNS to an astrocytic fate, Here we show that C NTF causes activation of janus kinase-signal transducers and activator s of transcription and mitogen-activated protein kinase (MAPK) pathway s with differential kinetics in these cells. Inhibition studies indica te that activation of the MAPK pathway is required early in the differ entiation process, whereas activation of signal transducer and activat or of transcription (STAT) proteins is required for commitment to an a strocytic fate. Bone morphogenetic proteins have also been shown to ca use astrocytic differentiation but do not cause STAT activation or ast rocytic differentiation in fibroblast growth factor 2-expanded fetal s tem cells used here. These results show that there are two distinct ro utes to initiate astrocytic commitment in multipotent CNS precursors.