ABSTRACT
Visual circuit development is characterized by subdivision of neuropils into layers that house distinct sets of synaptic connections. We find that, in the Drosophila medulla, this layered organization depends on the axon guidance regulator Plexin A. In Plexin A null mutants, synaptic layers of the medulla neuropil and arborizations of individual neurons are wider and less distinct than in controls. Analysis of semaphorin function indicates that Semaphorin 1a, acting in a subset of medulla neurons, is the primary partner for Plexin A in medulla lamination. Removal of the cytoplasmic domain of endogenous Plexin A has little effect on the formation of medulla layers; however, both null and cytoplasmic domain deletion mutations of Plexin A result in an altered overall shape of the medulla neuropil. These data suggest that Plexin A acts as a receptor to mediate morphogenesis of the medulla neuropil, and as a ligand for Semaphorin 1a to subdivide it into layers. Its two independent functions illustrate how a few guidance molecules can organize complex brain structures by each playing multiple roles.
Footnotes
Author contributions
Conceptualization: M.E.B., J.D., S.A., J.E.T.; Methodology: M.E.B.; Formal analysis: M.E.B., J.D.; Investigation: M.E.B., J.D., S.A.; Writing - original draft: M.E.B.; Writing - review & editing: J.D., S.A., J.E.T.; Supervision: J.E.T.; Project administration: J.E.T.; Funding acquisition: J.D., J.E.T.
Funding
This work was supported by the National Institutes of Health (R01 NS112211 to J.E.T. with supplement NS112211-02S1 to M.E.B., and fellowship F31 EY025568 to J.D.). Deposited in PMC for release after 12 months.
Data availability
All relevant data can be found within the article and its supplementary information.
