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Originally published as Genetics Published Articles Ahead of Print on February 16, 2005.

Genetics, Vol. 170, 149-159, May 2005, Copyright © 2005
doi:10.1534/genetics.104.036863

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Slit-Roundabout Signaling Neutralizes Netrin-Frazzled-Mediated Attractant Cue to Specify the Lateral Positioning of Longitudinal Axon Pathways

Krishna Moorthi Bhat1

Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322

1 Address for correspondence: Department of Cell Biology, 413 Whitehead Biomedical Research Bldg., 415 Michael St., Emory University School of Medicine, Atlanta, GA 30322.
E-mail: kbhat{at}cellbio.emory.edu

An extending axon growth cone is subjected to attractant and repellent cues. It is not clear how these growth cones discriminate the two opposing forces and select their projection paths. Here, we report that in the Drosophila nerve cord the growth cones of longitudinal tracts are subjected to attraction by the Netrin-Frazzled pathway. However, the midline Slit neutralizes this pathway in a Robo-dependent manner and prevents Netrin-Frazzled-mediated attraction of longitudinal tracts. Our results suggest that the loss of a neutralizing effect on the Netrin-mediated attraction is responsible for the longitudinal tracts entering the midline in slit mutants as opposed to a loss of repulsion as is currently believed. This effect is not via a direct inhibition of Frazzled by Robo; instead, it is at a level downstream of Frazzled. Thus, the growth cones of longitudinal tracts subjected to two opposing forces are able to block one with the other and specify their correct lateral positioning along the midline.




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