Slit-roundabout signaling neutralizes netrin-Frazzled-mediated attractant cue to specify the lateral positioning of longitudinal axon pathways.
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.
Bhat
Krishna Moorthi
KM
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.
D000818:Animals; D001369:Axons / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004843:Epistasis, Genetic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075388:Netrin-1; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D025521:Tumor Suppressor Proteins; D000097905:Roundabout Proteins; C000617310:fra protein, Drosophila; C066819:sli protein, Drosophila
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