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First published online 22 November 2006
doi: 10.1242/dev.02653

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02653v1 dev.02653v2 134/2/273    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garbe, D. S. Articles by Bashaw, G. J. Search for Related Content PubMed PubMed Citation Articles by Garbe, D. S. Articles by Bashaw, G. J.

ß-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS

¹ Department of Neuroscience, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
² Program in Cell and Developmental Biology, and Department of Biological Sciences, University of Illinois Chicago, Chicago, IL 60607, USA.

^* Author for correspondence (e-mail: gbashaw{at}mail.med.upenn.edu)

Accepted 19 September 2006

- and ß-Spectrin are major components of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins. Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation. Here, we demonstrate that ß-Spectrin is required in neurons for proper midline axon guidance in the Drosophila embryonic CNS. In ß-spectrin mutants many axons inappropriately cross the CNS midline, suggesting a role for ß-Spectrin in midline repulsion. Surprisingly, neither the Ankyrin-binding nor the pleckstrin homology (PH) domains of ß-Spectrin are required for accurate guidance decisions. -Spectrin is dependent upon ß-Spectrin for its normal subcellular localization and/or maintenance, whereas -spectrin mutants exhibit a redistribution of ß-Spectrin to the axon scaffold. ß-spectrin mutants show specific dose-dependent genetic interactions with the midline repellent slit and its neuronal receptor roundabout (robo), but not with other guidance molecules. The results suggest that ß-Spectrin contributes to midline repulsion through the regulation of Slit-Robo pathway components. We propose that the Spectrin network is playing a role independently of Ankyrin in the establishment and/or maintenance of specialized membrane domains containing guidance molecules that ensure the fidelity of axon repulsion at the midline.

Key words: Axon guidance, Midline, Repulsion, Roundabout, Slit, Spectrin, Ankyrin, Drosophila

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