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Genetic analysis of EphA-dependent signaling mechanisms controlling topographic mapping in vivo
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. (Kullander)
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2006 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 133, no 22, 4415-4420 p.Article in journal (Refereed) Published
Abstract [en]

Ephrin/Eph ligands and receptors are best known for their prominent role in topographic mapping of neural connectivity. Despite the large amount of work centered on ephrin/Eph-dependent signaling pathways in various cellular contexts, the molecular mechanisms of action of Eph receptors in neural mapping, requiring dynamic interactions between complementary gradients of ephrins and Eph receptors, remain largely unknown. Here, we investigated in vivo the signaling mechanisms of neural mapping mediated by the EphA4 receptor, previously shown to control topographic specificity of thalamocortical axons in the mouse somatosensory system. Using axon tracing analyses of knock-in mouse lines displaying selective mutations for the Epha4 gene, we determined for the first time which intracellular domains of an Eph receptor are required for topographic mapping. We provide direct in vivo evidence that the tyrosine kinase domain of EphA4, as well as a tight regulation of its activity, are required for topographic mapping of thalamocortical axons, whereas non-catalytic functional modules, such as the PDZ-binding motif (PBM) and the Sterile-alpha motif (SAM) domain, are dispensable. These data provide a novel insight into the molecular mechanisms of topographic mapping, and constitute a physiological framework for the dissection of the downstream signaling cascades involved.

Place, publisher, year, edition, pages
2006. Vol. 133, no 22, 4415-4420 p.
Keyword [en]
topographic mapping, ephrin, Eph, thalamocortical
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-14474DOI: 10.1242/dev.02623ISI: 000241857500004PubMedID: 17035292OAI: oai:DiVA.org:uu-14474DiVA: diva2:42244
Available from: 2008-01-30 Created: 2008-01-30 Last updated: 2011-05-12Bibliographically approved

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