Semaphorin 1a-mediated dendritic wiring of the Drosophila mushroom body extrinsic neurons

Abstract

Significance The adult Drosophila mushroom body (MB) is one of the most extensively studied neural circuits. However, how its circuit organization is established during development is unclear. In this study, we provide an initial characterization of the assembly process of the extrinsic neurons (dopaminergic neurons and MB output neurons) that target the vertical MB lobes. We probe the cellular mechanisms guiding the neurite targeting of these extrinsic neurons and demonstrate that Semaphorin 1a is required in several MB output neurons for their dendritic innervations to three specific MB lobe zones. Our study reveals several intriguing molecular and cellular principles governing assembly of the MB circuit.

Hacking brain development to test models of sensory coding

“…γ2,α'1 MBON dendrites were seen throughout the γ lobe in the transverse plane and slightly extended along the lobe in the coronal z-projection (Figure 6G). Consistent with a recent study of MBON morphology in HU-fully ablated animals, we also observed γ2,α'1 MBON dendrites to arborize more sparsely in the lobes, with slight extension outside the lobes (Lin et al, 2022).…”

The making of the Drosophila mushroom body

“…As indicated previously, the MBONs and DANs innervating the adult vertical lobes are mostly incorporated into the MB network during metamorphosis (Truman et al, 2022). Recently, my team followed the development of these extrinsic neurons during the pupal stage and found that their axons or dendrites sequentially innervate the MB zones in a stereotyped pattern (Lin et al, 2022). In general, innervation by the DAN axons initiates from the zones near the base of the vertical lobes and finishes at the tips of the vertical lobes, whereas the MBON dendrites innervate from the opposite direction, i.e., from the tips to the base.…”

“…In contrast to the dispensable role of neighboring MBONs and DANs, KC axons are necessary for the correct arborization patterns of both MBON dendrites and DAN axons. In alpha lobe absent (ala) mutant flies in which the MB vertical lobes are absent, most MBON dendrites and DAN axons that normally target the vertical lobes wander around the missing lobes (Pascual and Preat, 2001;Pascual et al, 2005;Lin et al, 2022). Strikingly, when their usual target zone in the α′ lobe is missing, the MBON-α′2 dendrites steer away to innervate the β′2 zone of the horizontal lobes (a less prominent ectopic innervation is also found in an α′-like zone).…”

“…Consistently, knockdown of sema1a in MBONs that normally project to these three zones results in significant dendritic innervation defects. Therefore, ligands for Sema1a likely work in combination with distinct guidance cues in each of the three zones to organize the zonal-specific innervation patterns of the MBON dendrites (Lin et al, 2022). Sema1a represents the first guidance molecule to be discovered that instructs zonal targeting of MBON dendrites.…”

“…Identification of Sema1a ligands should provide insights into how the MB lobes are zonally patterned. Notably, the canonical ligands for Sema1a-Plexin A (PlexA), Sema2a, and Sema2b-do not appear to be required for MBON dendritic innervations (Cafferty et al, 2006;Sweeney et al, 2011;Jeong et al, 2012;Lin et al, 2022). No dendritic innervation defects have been observed for sema2a/2b double mutant flies or when plexA is knocked down panneuronally or in the glia.…”