Wiley, Developmental Neurobiology, p. NA-NA, 2009
DOI: 10.1002/dneu.20762
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The formation of neuronal networks, during development and regeneration, requires outgrowthof axons along reproducible paths towards their appropriate postsynaptic target cells. Axonalextension occurs at growth cones at the tips of axons. Growth cone advance and navigationrequires the activity of their cytoskeletal networks, comprising F-actin in lamellipodia andfilopodia as well as dynamic microtubules emanating from bundles of the axonal core. Themolecular mechanisms governing these two cytoskeletal networks, their cross-talk, and theirresponse to extracellular signalling cues are only partially understood, hindering our conceptual understanding of how regulated changes in growth cone behaviour are controlled.Here we introduce Drosophila growth cones as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila growth cones are similar to those of other models, including mammals, as demonstrated here for microtubule and F-actin dynamics, axonal growth rates, filopodial structure and motility, organisational principles of MT networks and subcellular marker localisation. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations we demonstrate a role of the actin cytoskeleton in a specific form of microtubule organisation (loop formation), known to regulate growth cone pausing behaviour. We demonstrate these events to be mediated by the actin-microtubule linking factor Short stop, thus identifying an essential molecular player in this context.