L1CAM/Neuroglian controls the axon-axon interactions establishing layered and lobular mushroom body architecture.
Bottom Line: We demonstrate that the Drosophila melanogaster L1CAM homologue Neuroglian mediates adhesion between functionally distinct mushroom body axon populations to enforce and control appropriate projections into distinct axonal layers and lobes essential for olfactory learning and memory.For functional cluster formation, intracellular Ankyrin2 association is sufficient on one side of the trans-axonal complex whereas Moesin association is likely required simultaneously in both interacting axonal populations.Together, our results provide novel mechanistic insights into cell adhesion molecule-mediated axon-axon interactions that enable precise assembly of complex neuronal circuits.
Affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland University of Basel, 4003 Basel, Switzerland.Show MeSH
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Mentions: To address potential functions of Nrg that may be masked by the hypomorphic nature of our extra- and intracellular mutations, we next analyzed MB neurons lacking all Nrg using the mosaic analysis with a repressible cell marker (MARCM) technique (Lee and Luo, 1999). Axons of nrg14 single cell mutant clones never failed to grow out or to enter the pedunculus, and we observed only minor branching defects in agreement with prior observations (Fig. 2, A–C, J; Goossens et al., 2011). To address whether Nrg is potentially required for the coordination of larger population of axons or for the interaction between axons of different identity, we next generated NB clones that either included only αβ neurons, both α′β′ and αβ neurons, or all three subtypes of MB neurons (Fig. 1 A). Interestingly, the majority of αβ NB clones did not show any alteration of axonal projections (Fig. 2, D, E, and J). However, in ∼20% of these clones, we observed defects including the formation of ball-like structures below the calyx resembling the phenotype of hypomorphic nrg mutations (Fig. 2, F and J). In contrast, 78% of NB clones that included α′β′ neurons in addition to αβ neurons showed striking defects in MB development, with mutant α′β′ and αβ axons projecting straight to the tip of the α-lobes. In these cases, axons take a shortcut and circumvent their normal path through the pedunculus and the lobes (Fig. 2, G–K). Interestingly, mutant γ axons projected appropriately through the pedunculus to the lobes (Fig. 2 I). These data indicate that Nrg is not required in single axons navigating into the MB structure but is required within populations of α′β′ and/or pioneering αβ axons that likely mediate an interaction between these two distinct axonal populations.
Affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland University of Basel, 4003 Basel, Switzerland.