RECIPROCAL REGULATION OF CILIARY NEUROTROPHIC FACTOR RECEPTORS AND ACETYLCHOLINE-RECEPTORS DURING SYNAPTOGENESIS IN EMBRYONIC CHICK ATRIA

Ciliary neurotrophic factor (CNTF) has been implicated in the developm ent, survival, and maintenance of a broad range of neurons and glia in the peripheral nervous system and the CNS. Evidence also suggests tha t CNTF may affect development of cells outside the nervous system. We have found that functional CNTF and its receptor are expressed in deve loping embryonic chick heart and may be involved in parasympathetic sy napse formation. CNTF and CNTF receptor mRNA levels were highest at em bryonic day 11 (E11)-E13, the period of parasympathetic innervation in chick atria. Levels of atrial CNTF receptor mRNA were fourfold greate r at E13 than at E6 and at E13 were 2.5-fold higher in atria than in v entricle, corresponding to the higher degree of parasympathetic innerv ation occurring in atria. Treatment of isolated atria or cultured atri al myocytes with recombinant human or avian CNTF resulted in the tyros ine phosphorylation and nuclear translocation of the signal transducer and activator of transcription STAT3. The developmental increase in a trial CNTF receptor mRNA was enhanced by stimulating muscarinic recept ors with carbachol in ovo and was inhibited by blocking muscarinic cho linergic receptors with atropine. Treatment of cultured atrial myocyte s with CNTF resulted in a twofold increase in the levels of muscarinic receptors. Thus, CNTF was able to regulate a key component of parasym pathetic synapses on atrial myocytes. These results suggest a postsyna ptic role for CNTF in the onset of parasympathetic function in the dev eloping heart and provide new clues to molecular mechanisms directing synapse formation at targets of the autonomic nervous system.