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: Based on the trans-axonal rescues of nrg14; P[nrg180_ΔFIGQY] mutants, we hypothesized that a major function of the Ank2 interaction may be clustering of Nrg, a feature that in principle can be accomplished with equal efficacy from either side of a trans-axonal interaction. If Nrg mediated axon–axon interactions depend on the formation of Nrg clusters, we would predict intragenic complementation between the three nrg mutations despite their unique cell type–specific requirements. Strikingly, while we observed identical phenotypes for all three mutations when homo/hemizygous (Fig. 8, A–C and G), all trans-heterozygous combinations restored pedunculus entry and at least partially rescued lobe formation (Fig. 8, D–G). These results provide strong evidence that multimeric clusters mediate Nrg function in vivo. These data further demonstrate that the NrgΔFERM protein is functional and that the intracellular FIGQY and FERM domains act independently of each other. The observed lobe formation defects in transheterozygous nrg849 and nrg14; P[nrg_ΔFERM] mutants were consistent with the more essential requirements of these two protein domains (Fig. 8, F and G). Together, these data demonstrate that the extra- and intracellular Nrg protein–protein interaction domains act in a cooperative manner during the cell type–specific axon–axon interactions necessary for the establishment of MB architecture (Fig. 8 H).
Affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland University of Basel, 4003 Basel, Switzerland.