The goal of this research is to identify a potentially novel neurotrophic factor which induces expression of the M2 muscarinic acetylcholine receptor (mAChR) gene in the chick retina, and to determine the mechanisms responsible for the differential regulation of mAChR expression during embryonic development of the chick retina. This research will use several purification methods to isolate the M2-inducing factor based on its ability to induce transcription of the M2 mAChR gene in cultured retinal neurons. This work will describe the differential expression of mAChRs by using subtype-specific antibodies to co-localize mAChRs with a variety of retinal cell markers during various stages of development. Finally, this work proposes to use pharmacologic inhibitors and dominant-negative signalling molecules to elucidate the signal transduction mechanisms utilized by the M2-inducing factor to induce transcription of the M2 mAChR gene. Taken together, these data will provide important new information on the mechanisms that control proper embryonic development of the neural retina.
Belmonte, K E; McKinnon, L A; Nathanson, N M (2000) Developmental expression of muscarinic acetylcholine receptors in chick retina: selective induction of M2 muscarinic receptor expression in ovo by a factor secreted by muller glial cells. J Neurosci 20:8417-25 |