The Netrin 1 Receptors Unc5h3 and Dcc Are Necessary at Multiple Choice Points for the Guidance of Corticospinal Tract Axons
| Autor: | Stefan Przyborski, Jacqueline H. Finger, Susan L. Ackerman, Rod Bronson, Belinda S. Harris, Kenneth O. Johnson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
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 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|