Motoneurons are key points of convergence within motor networks, acting as the "output channels" that directly control sets of muscles to maintain posture and generate movement. Here we use genetic mosaic techniques to reveal the origins and architecture of the leg motoneurons of Drosophila. We show that a small number of leg motoneurons are born in the embryo but most are generated during larval life. These postembryonic leg motoneurons are produced by five neuroblasts per hemineuromere, and each lineage generates stereotyped lineage-specific projection patterns. Two of these postembryonic neuroblasts generate solely motoneurons that are the bulk of the leg motoneurons. Within the largest lineage, lineage 15, we see distinct birth-order differences in projection patterns. A comparison of the central projections of leg motoneurons and the muscles they innervate reveals a stereotyped architecture and the existence of a myotopic map. Timeline analysis of axonal outgrowth reveals that leg motoneurons reach their sites of terminal arborization in the leg at the time when their dendrites are elaborating their subtype-specific shapes. Our findings provide a comprehensive description of the origin, development, and architecture of leg motoneurons that will aid future studies exploring the link between the assembly and organization of connectivity within the leg motor system of Drosophila.

During development of the Drosophila motor system, global guidance cues control and coordinate the targeting of both input and output elements of the neural system.

In this review, we emphasize the clinical relevance and potential translation of exploiting this oxidative DNA repair mechanism using synthetic lethality studies in MMR-deficient cells, to develop improved treatment strategies that will benefit cancer patients.

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