Differentiating neurons activate transcription of the brain lipid-binding protein gene in radial glia through a novel regulatory element.

Abstract

Formation and maintenance of a radial glial scaffold is fundamental for development of the vertebrate central nervous system. In mammals, radial glia arise in the neuroepithelium immediately prior to differentiation and migration of neurons away from the ventricular zones, and they are maintained until neuronal migration subsides. We have previously shown that expression of the brain lipid-binding protein (BLBP) in radial glia throughout the developing CNS is strictly correlated with the differentiation and migration of neurons upon these cells, and that BLBP function is required to maintain differentiation of primary cerebellar glial cells in vitro (Feng, L., Hatten, M. E. and Heintz, N. (1994). Neuron 12, 895-908). In this study, we demonstrate that BLBP transcription 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 demonstrate that BLBP expression in primary cerebellar glial cells requires coculture with differentiating neurons, and that this induction is regulated by the radial glia-specific element. The fact that transcription 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 differentiating neurons in the epigenetic regulation of radial glial cell function in vivo.