Homophilic Dscam interactions control complex dendrite morphogenesis.
Alternative splicing of the Drosophila gene Dscam results in up to 38,016 different receptor isoforms proposed to interact by isoform-specific homophilic binding. We report that Dscam controls cell-intrinsic aspects of dendrite guidance in all four classes of dendrite arborization (da) neurons. Loss of Dscam in single neurons causes a strong increase in self-crossing. Restriction of dendritic fields of neighboring class III neurons appeared intact in mutant neurons, suggesting that dendritic self-avoidance, but not heteroneuronal tiling, may depend on Dscam. Overexpression of the same Dscam isoforms in two da neurons with overlapping dendritic fields forced a spatial segregation of the two fields, supporting the model that dendritic branches of da neurons use isoform-specific homophilic interactions to ensure minimal overlap. Homophilic binding of the highly diverse extracellular domains of Dscam may therefore limit the use of the same "core" repulsion mechanism to cell-intrinsic interactions without interfering with heteroneuronal interactions.
Hughes
Michael E
ME
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Bortnick
Rachel
R
Tsubouchi
Asako
A
Bäumer
Philipp
P
Kondo
Masahiro
M
Uemura
Tadashi
T
Schmucker
Dietmar
D
D000818:Animals; D030801:Animals, Genetically Modified; D015815:Cell Adhesion Molecules; D002450:Cell Communication; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D009024:Morphogenesis; D009154:Mutation; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D020033:Protein Isoforms