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Science 324 (5929): 944-947

Copyright © 2009 by the American Association for the Advancement of Science

A Frazzled/DCC-Dependent Transcriptional Switch Regulates Midline Axon Guidance

Long Yang, David S. Garbe, Greg J. Bashaw*

Abstract: Precise wiring of the nervous system depends on coordinating the action of conserved families of proteins that direct axons to their appropriate targets. Slit-roundabout repulsion and netrin–deleted in colorectal cancer (DCC) (frazzled) attraction must be tightly regulated to control midline axon guidance in vertebrates and invertebrates, but the mechanism mediating this regulation is poorly defined. Here, we show that the Fra receptor has two genetically separable functions in regulating midline guidance in Drosophila. First, Fra mediates canonical chemoattraction in response to netrin, and, second, it functions independently of netrin to activate commissureless transcription, allowing attraction to be coupled to the down-regulation of repulsion in precrossing commissural axons.

Department of Neuroscience, University of Pennsylvania School of Medicine, 1113 BRB2/3, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: gbashaw{at}mail.med.upenn.edu


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