Altered branching of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin and dopamine.

The anatomy of peripheral serotonin-containing fibers (5-HT fibers) in the gut of wild-type Drosophila larvae was compared to mutants deficient in the gene that encodes the enzyme dopa decarboxylase (DfDdc mutants). The 5-HT fibers, located in the proventriculus and midgut, were visualized immunocytochemically by using a monoclonal antibody against 5-HT. Since DfDdc larvae are devoid of 5-HT and dopamine in the nervous system, the highly selective uptake capability of 5-HT neurons was used to visualize the 5-HT fibers. We found that the absence of 5-HT and dopamine in the nervous system of DfDdc animals does not prevent 5-HT fibers from reaching their appropriate targets. However, these fibers in the mutant show a 2-fold increase in the extent of branching. This effect is specific to 5-HT fibers, since glutamate-like and FMRFamide-like immunoreactive fibers of the proventriculus and midgut remain unaffected in the mutant. Low but detectable levels of dopamine and 5-HT in the CNS are sufficient to prevent the increase in arborization, as indicated by analyses of a temperature-sensitive Ddc allele (Ddcts2), which has very low dopa decarboxylase activity. The abnormally extensive branching of 5-HT fibers also can be partially rescued by feeding DfDdc larvae with dopamine. In contrast, feeding with a 5-HT-containing diet had no effect on the mutant phenotype. Hypotheses that could explain the mutant phenotype are proposed.