Axon sorting within the spinal cord marginal zone via Robo-mediated inhibition of N-cadherin controls spinocerebellar tract formation Journal Article
| Authors: | Sakai, N.; Insolera, R.; Sillitoe, R. V.; Shi, S. H.; Kaprielian, Z. |
| Article Title: | Axon sorting within the spinal cord marginal zone via Robo-mediated inhibition of N-cadherin controls spinocerebellar tract formation |
| Abstract: | The axons of spinal projection neurons transmit sensory information to the brain by ascending within highly organized longitudinal tracts. However, the molecular mechanisms that control the sorting of these axons within the spinal cord and their directed growth to poorly defined targets are not understood. Here, we show that an interplay between Robo and the cell adhesion molecule, N-cadherin, sorts spinal commissural axons into appropriate longitudinal tracts within the spinal cord, and thereby facilitates their brain targeting. Specifically, we show that d1 and d2 spinal commissural axons join the lateral funiculus within the spinal cord and target the cerebellum in chick embryos, and that these axons contribute to the spinocerebellar projection in transgenic reporter mice. Disabling Robo signaling or overexpressing N-cadherin on these axons prevents the formation of the lateral funiculus and the spinocerebellar tract, and simultaneously perturbing Robo and N-cadherin function rescues both phenotypes in chick embryos. Consistent with these observations, disabling Robo function in conditional N-cadherin knock-out mice results in a wild-type-like lateral funiculus. Together, these findings suggest that spinal projection axons must be sorted into distinct longitudinal tracts within the spinal cord proper to project to their brain targets. © 2012 the authors. |
| Keywords: | immunohistochemistry; controlled study; protein expression; mutation; nonhuman; mouse; phenotype; animals; mice; mice, knockout; animal tissue; cerebellum; embryo; animal experiment; nerve tissue proteins; genetic transfection; spinal cord; nerve cell adhesion molecule; electroporation; plasmids; cell count; functional laterality; cell adhesion; cadherins; rhombencephalon; axons; receptors, immunologic; chick embryo; chick; roundabout receptor; nerve fiber transport; neurogenin 1; cerebellar peduncle; epifluorescence microscopy; neuroanatomical tract tracing; rhombencephalic isthmus; spinocerebellar tract; receptors, dopamine d1; receptors, dopamine d2; spinocerebellar tracts |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 32 |
| Issue: | 44 |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Date Published: | 2012-10-31 |
| Start Page: | 15377 |
| End Page: | 15387 |
| Language: | English |
| DOI: | 10.1523/jneurosci.2225-12.2012 |
| PROVIDER: | scopus |
| PMCID: | PMC3511830 |
| PUBMED: | 23115176 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: JNRSD" - "Source: Scopus" |
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