Development of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin

We have initiated a study of the CNS of mutant Drosophila melanogaster larvae carrying a genetic deletion of the gene Ddc that encodes the enzyme dopa decarboxylase (DDC). The two major objectives of this study were (1) to ascertain that the DDC encoded by the gene Ddc was the only decarboxylase utilized in serotonin (5HT)-containing neurons and (2) to determine the effect of DDC deficiency on the development of 5HT-immunoreactive neurons. CNSs of wild-type larvae and of larvae genetically deficient for the gene Ddc were processed for serotonin immunocytochemistry using a monoclonal antibody against 5HT. The pattern of 5HT immunoreactivity in the wild-type and the Ddc-deficient CNS is compared. In contrast to the wild-type, 5HT immunoreactivity is absent in the Ddc-deficient CNSs. The lack of immunocytochemically detectable 5HT in the mutant CNSs is consistent with the idea that the DDC encoded by the gene Ddc is utilized in 5HT-containing neurons. To study the development of neurons committed to the 5HT differentiation pathway in the absence of 5HT, we used a second biochemical property characteristic of 5HT-containing neurons, the ability to take up 5HT. CNSs from mutant animals were incubated in exogenous 5HT and the accumulated 5HT detected immunocytochemically. Neurons capable of selective 5HT uptake were present in the mutant CNSs in the same pattern as the 5HT-immunoreactive neurons in the wild-type CNS. This result suggests that the presumed inability to synthesize 5HT does not preclude differentiation of other normal biochemical properties of 5HT-containing neurons.