MOLECULAR-BASIS FOR DIFFERENTIAL EXPRESSION OF GLUTAMINE-SYNTHETASE IN RETINA GLIA AND NEURONS

Glutamine synthetase (GS) is a differentiation marker of retina glial cells. It is expressed in the chicken neural retina at a particularly high level, is inducible by glucocorticoids and is always confined to Muller glia. This study investigated the molecular basis for tissue and cell-type specific expression of the GS gene. A high level of os expression in the retina was found to coincide with the accumulation of a relatively high lever of GS mRNA in this tissue. The gliatoxic agent alpha-aminoadipic acid, which can selectively destroy glia cells, was used to demonstrate that restriction of os induction to Muller glia is controlled at a transcriptional level. Cortisol could induce accumulation of GS mRNA and transcription of the GS gene in Muller glia but not in retina neurons. Glia and neurons were also found to differ in their ability to express the glucocorticoid inducible CAT construct, p Delta G46TCO, which is controlled by a 'simple GRE' promoter. When introduced into cells of retina tissue, this construct was cortisol-inducible in glia whereas in neurons it was only slightly inducible or not at all. Introduction of a glucocorticoid receptor expression vector into the cells facilitated induction of the CAT construct in neurons. Analysis by immunoblotting revealed that expression of the glucocorticoid receptor protein is predominantly restricted to Muller glia. These results suggest that differential levels of glucocorticoid receptor expression in glia and neurons might be the basis for cell-type specific induction of GS.