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 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.
Zhan
Xiao-Li
XL
Howard Hughes Medical Institute, Department of Biological Chemistry, The David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
Clemens
James C
JC
Neves
Guilherme
G
Hattori
Daisuke
D
Flanagan
John J
JJ
Hummel
Thomas
T
Vasconcelos
M Luisa
ML
Chess
Andrew
A
Zipursky
S Lawrence
SL
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D024521:Mushroom Bodies / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D020033:Protein Isoforms; D011506:Proteins