title: Cell-specific alternative splicing of Drosophila Dscam2 is crucial for proper neuronal wiring.
abstract: How a finite number of genes specify a seemingly infinite number of neuronal connections is a central question in neurobiology. Alternative splicing has been proposed to increase proteome diversity in the brain. Here we show that cell-specific alternative splicing of a cell-surface protein is crucial for neuronal wiring. Down syndrome cell adhesion molecule 2 (Dscam2) is a conserved homophilic binding protein that can induce repulsion between opposing neurons. In the fly visual system, L1 and L2 neurons both require Dscam2 repulsion, but paradoxically, they also physically contact each other. We found that the cell-specific expression of two biochemically distinct alternative isoforms of Dscam2 prevents these cells from repelling each other. Phenotypes were observed in the axon terminals of L1 and L2 when they expressed the incorrect isoform, demonstrating a requirement for distinct isoforms. We conclude that cell-specific alternative splicing is a mechanism for achieving proper connectivity between neurons.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Grace Ji-Eun
authors.initials: GJ
authors.lastname: Lah
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Joshua Shing Shun
authors.initials: JS
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: s.millard@uq.edu.au.
authors.forename: S Sean
authors.initials: SS
authors.lastname: Millard
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D019006:Neural Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D029721:Drosophila Proteins; C520675:Dscam2 protein, Drosophila; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms