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The Journal of Neuroscience, November 15, 2000, 20(22):8417-8425

Developmental Expression of Muscarinic Acetylcholine Receptors in Chick Retina: Selective Induction of M2 Muscarinic Receptor Expression In Ovo by a Factor Secreted by Müller Glial Cells

Kristen E. Belmonte, Lise A. McKinnon, and Neil M. Nathanson

Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195-7750

Muscarinic acetylcholine receptors (mAChRs) play an important role in signal processing in the retina. We have used subtype-specific antibodies to identify the changes in the localization of mAChR expression during embryonic development of the retina in vivo and their relationship to the changes in mAChRs in retinal cells in culture. We have demonstrated previously that treatment of fresh retinal cultures with conditioned media from mature retinal cultures specifically induces expression of the M2 mAChR (McKinnon et al., 1998). We show that the M2-inducing activity, which we tentatively have called MARIA (muscarinic acetylcholine receptor-inducing activity) is produced by Müller glial cells in culture, because significant activity can be found in media conditioned by essentially neuron-free cultures of Müller glia, as well as by a Müller glial cell line but not several neuroblastoma cell lines. We also demonstrate that the appearance of the M2 receptor in vivo occurs concomitantly with the appearance of significant numbers of Müller glial cells in the developing retina. Furthermore, the administration of crude or partially purified preparations of MARIA to developing chick embryos in ovo induces precocious expression of M2 mAChRs in the appropriate cell types in the retina. These results show that a factor secreted by cultured retinal Müller glia can regulate M2 mAChR expression in vivo and in vitro and suggest that the secretion of MARIA by Müller glia in vivo may be responsible for the normal induction of M2 mAChR expression during embryonic development.

Key words: muscarinic; Müller glia; reporter gene; retina; chick; development; neurotrophic factor


Copyright © 2000 Society for Neuroscience  0270-6474/00/20228417-09$05.00/0


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