Molecular basis for differential expression of glutamine synthetase in retina glia and neurons

Rachel Grossman, Lyle E. Fox, Rena Gorovits, Iris Ben-Dror, Smadar Reisfeld, Lily Vardimon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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 Müller glia. This study investigated the molecular basis for tissue and cell-type specific expression of the GS gene. A high level of GS expression in the retina was found to coincide with the accumulation of a relatively high level of GS mRNA in this tissue. The gliatoxic agent α-aminoadipic acid, which can selectively destroy glia cells, was used to demonstrate that restriction of GS induction to Müller glia is controlled at a transcriptional level. Cortisol could induce accumulation of GS mRNA and transcription of the GS gene in Müller glia but not in retina neurons. Glia and neurons were also found to differ in their ability to express the glucocorticoid inducible CAT construct, pΔG46TCO, 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 Müller 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.

Original languageAmerican English
Pages (from-to)312-320
Number of pages9
JournalMolecular Brain Research
Volume21
Issue number3-4
DOIs
StatePublished - Feb 1994
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments. Part of the studies described in this manuscript were carried out in the laboratory of Dr. A.A. Moscona at the University of Chicago. We thank Dr. K.R. Yamamoto for the plasmids p6RGR and pG46TCO, Dr. J.B. Dodgson for the plasmid pPE5-0.3, Dr. J.D. Engel for the plasmid pCH3dR1 and Dr. H. Westphal for the monoclonal antibody GR 49-4. We are grateful to Dr. A.A. Moscona for critical reading of the manuscript. This work was supported by Grant 1-FY93-0582 from the March of Dimes Birth Defects Foundation, by The Israel Ministry of Science and Technology and the Israel Cancer Research Foundation. S.R. is the recipient of the Eshkol Fellowship from the Israel Ministry of Science and Technology.

Keywords

  • Embryonic development
  • Glucocorticoid receptor
  • Glutamine synthetase
  • Hormonal induction
  • Müller glia
  • Neural retina

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