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
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