Acetylcholinesterase mutants in Drosophila and their effects on the structure and function of the central nervous system.

Abstract

Mutations that eliminate acetylcholinesterase (AChE) activity were used to study the effects of disrupted acetylcholine metabolism on the form and function of the central nervous system in Drosophila melanogaster. Mutants in the Ace gene, which have no AChE activity, usually die in early development, but the postembryonic effects of this lesion can be studied in genetic mosaics, or with conditional mutants. Adult mosaics, which expressed Ace mutations in part of their CNS, exhibited morphological defects in any ganglionic neuropile whose cells were mutant. The defects included reduction in ganglionic volume, a condensed appearance, and for a very large clone, degeneration. Examination of many such mosaics indicated that small clones restricted to one side of the CNS were not usually lethal. However, mosaics with large clones, with clones on either side of the posterior slope of the protocerebrum, or with clones encompassing symmetrical structures on both sides of the CNS rarely survived to adulthood. Mosaics with AChE-null tissue on either side of the optic lobes or the posterior-inferior protocerebrum had marked deficits in optomotor behavior, although they were outwardly normal in their movement and posture. Mosaics with Ace mutant tissue in the first-order optic lobe, the lamina, lacked a synaptic component of the electroretinogram, the "off" transient. Tests of courtship behavior revealed that AChE mosaics with mutant clones in the superior protocerebrum were often capable of demonstrating male courtship. However, their behavior was quantitatively and perhaps qualitatively deficient. In order to study critical periods for the effects of mutant AChE, temperature-sensitive mutations of the Ace gene were isolated. Flies bearing certain of these new mutations produced AchE activity that was thermolabile in vivo and in vitro. The critical period during which the mutants were most susceptible to conditional lethality was late in embryogenesis.