title: Probabilistic splicing of Dscam1 establishes identity at the level of single neurons.
abstract: The Drosophila Dscam1 gene encodes a vast number of cell recognition molecules through alternative splicing. These exhibit isoform-specific homophilic binding and regulate self-avoidance, the tendency of neurites from the same cell to repel one another. Genetic experiments indicate that different cells must express different isoforms. How this is achieved is unknown, as expression of alternative exons in vivo has not been shown. Here, we modified the endogenous Dscam1 locus to generate splicing reporters for all variants of exon 4. We demonstrate that splicing does not occur in a cell-type-specific fashion, that cells sharing the same anatomical location in different individuals express different exon 4 variants, and that the splicing pattern in a given neuron can change over time. We conclude that splicing is probabilistic. This is compatible with a widespread role in neural circuit assembly through self-avoidance and is incompatible with models in which specific isoforms of Dscam1 mediate homophilic recognition between processes of different cells.
authors.affiliation: Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Satoru K
authors.initials: SK
authors.lastname: Miura
authors.forename: André
authors.initials: A
authors.lastname: Martins
authors.forename: Kelvin X
authors.initials: KX
authors.lastname: Zhang
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.forename: S Lawrence
authors.initials: SL
authors.lastname: Zipursky
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D011336:Probability; D020033:Protein Isoforms / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D020033:Protein Isoforms