The neurotrophin DNT-2 via the Toll-2 receptor regulates neuronal survival and morphology during visual system development.

During vertebrate nervous system development, neurons are produced in excess, and those receiving neurotrophin ligands are maintained, enabling neural circuit establishment. An apoptotic wave sweeps across the Drosophila pupal visual system, but whether neurotrophins participate in forming adult visual circuits remains unknown. Here, we show that Drosophila neurotrophin-3 (spz-3) and DNT-2 (spz-5) are expressed in retinal cells and medulla neurons and Toll receptors across the visual system. Using loss- and gain-of-function conditions for DNT-3 (spz-3) and DNT-2 (spz-5), we show that they both can, and are required to, promote cell survival. Importantly, genetic interaction data show that DNT-2 can function together with Toll-2. DNT-2 neurons were identified as medulla Mi1 neurons that connect to lamina L1 neurons expressing Toll-2. Loss of function for DNT-2 or Toll-2 induced apoptosis, and Toll-2 knock-down prevented the pro-survival function of DNT-2. DNT-2 overexpression resulted in excess Toll-2 neurons, whereas most Toll-2 neurons were lost in DNT-2 mutants. Furthermore, DNT-2 and Toll-2 were required for appropriate L1 axonal columnar organisation and dendritic morphology. Altogether, evolutionarily conserved neurotrophin family ligands control neuronal number through Toll receptors during visual circuit development in Drosophila.