On the role of normal acetylcholine metabolism in the formation and maintenance of the Drosophila nervous system.

We have examined the requirement for normal acetylcholine metabolism in the formation and maintenance of the larval and adult central nervous system in Drosophila melanogaster. By using mutations at the Ace and Cha loci, which respectively encode the degradative and synthetic enzymes for acetylcholine (ACh), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT), we have been able to disrupt acetylcholine metabolism in situ. An ultrastructural analysis of embryonic nervous tissue lacking either enzymatic function has indicated that while neither function is required for the formation of the larval central nervous system, each is required for the subsequent maintenance of its structural integrity and function. Using temperature sensitive mutations at the Cha locus, the normal developmental profile of ChAT activity during the late larval and pupal stages was disrupted. Subsequent examination of the morphology and behavior of the treated animals has indicated that normal acetylcholine metabolism is not required for the initial formation of the adult nervous system, but is required for the subsequent maintenance of its structural integrity and function. The results obtained in these studies are discussed with respect to data presented on the adult distribution of the cholinergic markers' AChE activity and ChAT immunoreactivity. The projections of adult peripheral neurons innervating Ace+ tissue from Ace cuticular clones has been examined to address the nature of the structure of Ace neuropil. Normal projections are apparently achieved and maintained, suggesting that the defects seen in adult Ace mosaics arise as an aberrant intracellular organization of morphologically normal cells.