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The Netrin 1 Receptors Unc5h3 and Dcc Are Necessary at Multiple Choice Points for the Guidance of Corticospinal Tract Axons
- Publication Year :
- 2002
- Publisher :
- Society for Neuroscience, 2002.
-
Abstract
- Migrating axons require the correct presentation of guidance molecules, often at multiple choice points, to find their target. Netrin 1, a bifunctional cue involved in both attracting and repelling axons, is involved in many cell migration and axon pathfinding processes in the CNS. The netrin 1 receptor DCC and its Caenorhabditis elegans homolog UNC-40 have been implicated in directing the guidance of axons toward netrin sources, whereas the C. elegans UNC-6 receptor, UNC-5 is necessary for migrations away from UNC-6. However, a role of vertebrate UNC-5 homologs in axonal migration has not been demonstrated. We demonstrate that the Unc5h3 gene product, shown previously to regulate cerebellar granule cell migrations, also controls the guidance of the corticospinal tract, the major tract responsible for coordination of limb movements. Furthermore, we show that corticospinal tract fibers respond differently to loss of UNC5H3. In addition, we observe corticospinal tract defects in mice homozygous for a spontaneous mutation that truncates the Dcc transcript. Postnatal day 0 netrin 1 mutant mice also demonstrate corticospinal tract abnormalities. Last, interactions between the Dcc and Unc5h3 mutations were observed in gene dosage experiments. This is the first evidence of an involvement in axon guidance for any member of the vertebrate unc-5 family and confirms that both the cellular and axonal guidance functions of C. elegans unc-5 have been conserved in vertebrates.
- Subjects :
- Gene Dosage
Pyramidal Tracts
Mice, Inbred Strains
Receptors, Cell Surface
Nervous System Malformations
Mice
Mice, Neurologic Mutants
Netrin
medicine
Animals
Nerve Growth Factors
ARTICLE
Caenorhabditis elegans Proteins
Caenorhabditis elegans
In Situ Hybridization
Pyramidal tracts
biology
General Neuroscience
Tumor Suppressor Proteins
fungi
Cell migration
Netrin-1
Granule cell
biology.organism_classification
DCC Receptor
Immunohistochemistry
Axons
Posterior Horn Cells
Rhombencephalon
medicine.anatomical_structure
Nerve growth factor
nervous system
Corticospinal tract
Calcium-Calmodulin-Dependent Protein Kinases
Axon guidance
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Netrin Receptors
Neuroscience
Cell Adhesion Molecules
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0b4a8c139c0da05c8de354f0596c0dd4