DIFFERENTIATING NEURONS ACTIVATE TRANSCRIPTION OF THE BRAIN LIPID-BINDING PROTEIN GENE IN RADIAL GLIA THROUGH A NOVEL REGULATORY ELEMENT

Formation and maintenance of a radial glial scaffold is fundamental fo r development of the vertebrate central nervous system. In mammals, ra dial glia arise in the neuroepithelium immediately prior to differenti ation and migration of neurons away from the ventricular zones, and th ey are maintained until neuronal migration subsides. We have previousl y shown that expression of the brain lipid-binding protein (BLBP) in r adial glia throughout the developing CNS is strictly correlated with t he differentiation and migration of neurons upon these cells, and that BLBP function is required to maintain differentiation of primary cere bellar glial cells in vitro (Feng, L., Hatten, M. E. and Heintz, N. (1 994), Neuron 12, 895-908). In this study, we demonstrate that BLBP tra nscription in vivo involves multiple regulatory elements, and that the dynamic temporal and spatial pattern of BLBP expression in radial and Bergmann glial cells throughout the developing CNS is programmed by a single radial glial cell-specific element (RGE). Furthermore, we demo nstrate that BLBP expression in primary cerebellar glial cells require s coculture with differentiating neurons, and that this induction is r egulated by the radial glia-specific element. The fact that transcript ion of BLBP in response to neurons in vitro and its dynamic regulation in radial glia throughout the CNS in vivo are both controlled by the RGE provides the first direct evidence supporting a role for different iating neurons in the epigenetic regulation of radial glial cell funct ion in vivo.