Nuclear factor-I regulates glial fibrillary acidic protein gene expression in astrocytes differentiated from cortical precursor cells
Article first published online: 5 APR 2006
Journal of Neurochemistry
Volume 97, Issue 4, pages 1057–1070, May 2006
How to Cite
Cebolla, B. and Vallejo, M. (2006), Nuclear factor-I regulates glial fibrillary acidic protein gene expression in astrocytes differentiated from cortical precursor cells. Journal of Neurochemistry, 97: 1057–1070. doi: 10.1111/j.1471-4159.2006.03804.x
- Issue published online: 5 APR 2006
- Article first published online: 5 APR 2006
- Received October 7, 2005; revised manuscript received December 30, 2005; accepted January 20, 2006.
- astrocyte differentiation;
- ciliary neurotrophic factor;
- neural progenitor cells;
- pituitary adenylate cyclase-activating polypeptide;
- process outgrowth;
- transcription factors
The elucidation of the transcriptional mechanisms that regulate glial fibrillary acidic protein (GFAP) gene expression is important for the understanding of the molecular mechanisms that control astrocyte differentiation during brain development. We investigated regulatory elements located in a proximal region of the GFAP promoter, important for expression in cortical precursor cells differentiating into astrocytes. One of these elements recognizes transcription factors of the nuclear factor-I family (NFI). We found that, in primary cultures of cortical cells, NFI occupies the GFAP promoter prior to the induction of astrocyte differentiation. In the developing cerebral cortex, the onset of expression of NFI coincides chronologically with the beginning of astrocytogenesis. Mutational analysis of the GFAP gene and transfections in primary cortical precursors show that inhibition of binding of NFI to the GFAP promoter results in decreased levels of transcriptional activity and is required for the synergistic stimulation of the GFAP promoter by the astrogenic agents, pituitary adenylate cyclase-activating polypeptide and ciliary neurotrophic factor, which in combination enhance astrocyte differentiation to generate astrocytes with longer processes. Thus, NFI appears to be an important factor for the integration of astrogenic stimuli in the developing central nervous system.