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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}

Netrin-DCC Signaling Regulates Corpus Callosum Formation Through Attraction of Pioneering Axons and by Modulating Slit2-Mediated Repulsion.
T. Fothergill, A.-L. S. Donahoo, A. Douglass, O. Zalucki, J. Yuan, T. Shu, G. J. Goodhill, and L. J. Richards (2014)
Cereb Cortex 24, 1138-1151
   Abstract »    Full Text »    PDF »
Netrin and Frazzled Regulate Presynaptic Gap Junctions at a Drosophila Giant Synapse.
B. O. Orr, M. A. Borgen, P. M. Caruccio, and R. K. Murphey (2014)
J. Neurosci. 34, 5416-5430
   Abstract »    Full Text »    PDF »
Distinct functional domains of the Abelson tyrosine kinase control axon guidance responses to Netrin and Slit to regulate the assembly of neural circuits.
M. P. O'Donnell and G. J. Bashaw (2013)
Development 140, 2724-2733
   Abstract »    Full Text »    PDF »
Src Inhibits Midline Axon Crossing Independent of Frazzled/Deleted in Colorectal Carcinoma (DCC) Receptor Tyrosine Phosphorylation.
M. P. O'Donnell and G. J. Bashaw (2013)
J. Neurosci. 33, 305-314
   Abstract »    Full Text »    PDF »
N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors.
Q. Chen, X. Sun, X.-h. Zhou, J.-h. Liu, J. Wu, Y. Zhang, and J.-h. Wang (2013)
J. Cell Sci. 126, 186-195
   Abstract »    Full Text »    PDF »
Amyloid Precursor Protein Regulates Netrin-1-mediated Commissural Axon Outgrowth.
N. Rama, D. Goldschneider, V. Corset, J. Lambert, L. Pays, and P. Mehlen (2012)
J. Biol. Chem. 287, 30014-30023
   Abstract »    Full Text »    PDF »
Cellular Strategies of Axonal Pathfinding.
J. Raper and C. Mason (2010)
Cold Spring Harb Perspect Biol 2, a001933
   Abstract »    Full Text »    PDF »
Navigating Intermediate Targets: The Nervous System Midline.
B. J. Dickson and Y. Zou (2010)
Cold Spring Harb Perspect Biol 2, a002055
   Abstract »    Full Text »    PDF »
Moving away from the midline: new developments for Slit and Robo.
A. R. Ypsilanti, Y. Zagar, and A. Chedotal (2010)
Development 137, 1939-1952
   Abstract »    Full Text »    PDF »
Drosophila Neurexin IV Interacts with Roundabout and Is Required for Repulsive Midline Axon Guidance.
S. Banerjee, K. Blauth, K. Peters, S. L. Rogers, A. S. Fanning, and M. A. Bhat (2010)
J. Neurosci. 30, 5653-5667
   Abstract »    Full Text »    PDF »
Crossing the Line.
T. Kidd (2009)
Science 324, 893-894
   Abstract »    Full Text »    PDF »

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