期刊
CELL
卷 133, 期 7, 页码 1241-1254出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.05.030
关键词
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCRR NIH HHS [S10 RR022636-01A1, S10 RR022636, S10-RR22636] Funding Source: Medline
- NIGMS NIH HHS [T32-GM07499, T32 GM007499] Funding Source: Medline
- NIMH NIH HHS [R01 MH071404, R01 MH071404-03] Funding Source: Medline
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.
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