The Role of Drosophila Neurexin-1 in Mushroom Body Development

Abstract

Neurexins are transmembrane adhesion proteins that have a demonstrated role in proper synaptic function and protein organization. Neurexin-deficient laboratory animals have behavioral and learning deficits. In humans, NRXN mutations cause, and increase the risk of, a wide range of neurocognitive disorders including autism, intellectual disability, and schizophrenia. Here I report on the effect of loss-of-function mutations in the single NRXN ortholog found in fruit flies, Drosophila neurexin-1 (dnrx), on neuronal morphology. Limited evidence has suggested that neurexins play a role in cytoskeletal organization and in regulating dendritogenesis. This study aimed to answer the question of whether or not neurexin proteins are necessary for the inherent morphological organization of the neuron. My results indicate that dnrx mutants display no overall structural defects in mushroom body (MB) morphology in vivo, but their MB neurons have distinct morphological features when cultured and analyzed in vitro. Quantitative analysis of cultured mutant pupal brain neurons revealed distinct alteration in morphology that was selective to MB γ-neurons. This change manifests itself in a significant increase in higher-order branching and branchpoint density. I also report here on a novel vacuole phenotype observed in the cell bodies of cultured neurons.