Analysis of Dscam Diversity in Regulating Axon Guidance in Drosophila Mushroom Bodies

Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the develo...

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Bibliographic Details
Published in:	Neuron (Cambridge, Mass.) Vol. 43; no. 5; pp. 673 - 686
Main Authors:	Zhan, Xiao-Li, Clemens, James C., Neves, Guilherme, Hattori, Daisuke, Flanagan, John J., Hummel, Thomas, Vasconcelos, M.Luisa, Chess, Andrew, Zipursky, S.Lawrence
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 02-09-2004 Elsevier Limited
Subjects:	Alternative Splicing - genetics Amino Acid Sequence - genetics Animals Animals, Genetically Modified Base Sequence - genetics Brain - cytology Brain - embryology Brain - metabolism Cell Adhesion Molecules Cell Communication - genetics Cell culture Cell Differentiation - genetics Drosophila Drosophila melanogaster - cytology Drosophila melanogaster - embryology Drosophila melanogaster - metabolism Drosophila Proteins Exons - genetics Gene Expression Regulation, Developmental - genetics Genes Growth Cones - metabolism Growth Cones - ultrastructure Insects Mammals Molecular Sequence Data Mushroom Bodies - cytology Mushroom Bodies - embryology Mushroom Bodies - metabolism Mutation - genetics Neurons Neurosciences Phenotype Protein Isoforms - genetics Protein Isoforms - metabolism Protein Structure, Tertiary - genetics Proteins Proteins - genetics Proteins - metabolism Scholarships & fellowships Transgenes - genetics
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Summary:	Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the precise spatiotemporal pattern of Dscam protein expression. We demonstrate that MB neurons express different arrays of Dscam isoforms and that single MB neurons express multiple isoforms. Two different Dscam isoforms differing in their extracellular domains introduced as transgenes into single mutant cells partially rescued the mutant phenotype. Expression of one isoform of Dscam in a cohort of MB neurons induced dominant phenotypes, while expression of a single isoform in a single cell did not. We propose that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0896-6273 1097-4199
DOI:	10.1016/j.neuron.2004.07.020