DSCAM is a netrin receptor that collaborates with DCC in mediating turning responses to netrin-1.
During nervous system development, spinal commissural axons project toward and across the ventral midline. They are guided in part by netrin-1, made by midline cells, which attracts the axons by activating the netrin receptor DCC. However, previous studies suggest that additional receptor components are required. Here, we report that the Down's syndrome Cell Adhesion Molecule (DSCAM), a candidate gene implicated in the mental retardation phenotype of Down's syndrome, is expressed on spinal commissural axons, binds netrin-1, and is necessary for commissural axons to grow toward and across the midline. DSCAM and DCC can each mediate a turning response of these neurons to netrin-1. Similarly, Xenopus spinal neurons exogenously expressing DSCAM can be attracted by netrin-1 independently of DCC. These results show that DSCAM is a receptor that can mediate turning responses to netrin-1 and support a key role for netrin/DSCAM signaling in commissural axon guidance in vertebrates.
Ly
Alice
A
Department of Molecular, Cellular, and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA.
Nikolaev
Anatoly
A
Suresh
Geetha
G
Zheng
Yufang
Y
Tessier-Lavigne
Marc
M
Stein
Elke
E
D000818:Animals; D001369:Axons / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014981:Xenopus
D008565:Membrane Proteins; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1