Cell-intrinsic requirement of Dscam1 isoform diversity for axon collateral formation.
The isoform diversity of the Drosophila Dscam1 receptor is important for neuronal self-recognition and self-avoidance. A canonical model suggests that homophilic binding of identical Dscam1 receptor isoforms on sister dendrites ensures self-avoidance even when only a single isoform is expressed. We detected a cell-intrinsic function of Dscam1 that requires the coexpression of multiple isoforms. Manipulation of the Dscam1 isoform pool in single neurons caused severe disruption of collateral formation of mechanosensory axons. Changes in isoform abundance led to dominant dosage-sensitive inhibition of branching. We propose that the ratio of matching to nonmatching isoforms within a cell influences the Dscam1-mediated signaling strength, which in turn controls axon growth and growth cone sprouting. Cell-intrinsic use of surface receptor diversity may be of general importance in regulating axonal branching during brain wiring.
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Haihuai
H
He
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium.
Yoshiaki
Y
Kise
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium.
Azadeh
A
Izadifar
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium.
Olivier
O
Urwyler
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium.
Derya
D
Ayaz
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Akhila
A
Parthasarthy
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium.
Bing
B
Yan
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium. Institute of Biochemistry, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
Maria-Luise
ML
Erfurth
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium.
Dan
D
Dascenco
Neuronal Wiring Laboratory, Vlaams Instituut voor Biotechnologie (VIB) Vesalius Research Center, 3000 Leuven, Belgium. Department of Oncology, School of Medicine, University of Leuven, 3000 Leuven, Belgium. dietmar.schmucker@vib-kuleuven.be.
Dietmar
D
Schmucker
D000483:Alleles; D000818:Animals; D001369:Axons / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development*; D018628:Gene Dosage; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D020033:Protein Isoforms