The expression of glial fibrillary acidic protein (GFAP), the major intermediate filament protein of mature astrocytes, is regulated under developmental and pathological conditions. Recently, we have investigated GFAP gene modulation by using a transgenic mouse bearing part of the GFAP gene promoter linked to the β-galactosidase reporter gene. We demonstrated that cerebral cortex neurons activate the GFAP gene promoter, inducing transforming growth factor-beta 1 (TGF-β1) secretion by astrocytes. Here, we report that cortical neurons or conditioned medium derived from them do not activate the GFAP gene promoter of transgenic astrocytes derived from midbrain and cerebellum suggesting a neuroanatomical regional specificity of this phenomenon. Surprisingly, they do induce synthesis of TGF-β1 by these cells. Western blot and immunocytochemistry assays revealed wild distribution of TGF receptor in all subpopulations of astrocytes and expression of TGF-β1 in neurons derived from all regions, thus indicating that the unresponsiveness of the cerebellar and midbrain GFAP gene to TGF-β1 is not due to a defect in TGF-β1 signalling. Together, our data highlight the great complexity of neuron–glia interactions and might suggest a distinct mechanism underlying modulation of the GFAP gene in the heterogeneous population of astrocytes throughout the central nervous system.