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Development. 2016 Mar 15;143(6):972-7. doi: 10.1242/dev.129684. Epub 2016 Feb 18.

Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila.

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MRC Centre for Developmental Neurobiology, New Hunts House, King's College, London, SE1 1UL, UK.
MSZ Universitat Würzburg, Versbacher Strasse 5, Würzberg 97078, Germany.
MRC Centre for Developmental Neurobiology, New Hunts House, King's College, London, SE1 1UL, UK
Howard Hughes Medical Institute, Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.


The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance.


Axon guidance; Drosophila; LIN-5; Midline; Mud; Netrin; NuMA

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