title: Filopodial dynamics and growth cone stabilization in Drosophila visual circuit development.
abstract: Filopodial dynamics are thought to control growth cone guidance, but the types and roles of growth cone dynamics underlying neural circuit assembly in a living brain are largely unknown. To address this issue, we have developed long-term, continuous, fast and high-resolution imaging of growth cone dynamics from axon growth to synapse formation in cultured Drosophila brains. Using R7 photoreceptor neurons as a model we show that >90% of the growth cone filopodia exhibit fast, stochastic dynamics that persist despite ongoing stepwise layer formation. Correspondingly, R7 growth cones stabilize early and change their final position by passive dislocation. N-Cadherin controls both fast filopodial dynamics and growth cone stabilization. Surprisingly, loss of N-Cadherin causes no primary targeting defects, but destabilizes R7 growth cones to jump between correct and incorrect layers. Hence, growth cone dynamics can influence wiring specificity without a direct role in target recognition and implement simple rules during circuit assembly.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States.|Division of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, Germany.|NeuroCure Cluster of Excellence, Charite Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Mehmet Neset
authors.initials: MN
authors.lastname: Özel
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Marion
authors.initials: M
authors.lastname: Langen
authors.affiliation: Center for the Biology of Disease, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.|Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium.
authors.forename: Bassem A
authors.initials: BA
authors.lastname: Hassan
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States.|Division of Neurobiology, Institute for Biology, Freie Universität Berlin, Berlin, Germany.|NeuroCure Cluster of Excellence, Charite Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: P Robin
authors.initials: PR
authors.lastname: Hiesinger
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology*; D061848:Optical Imaging; D011554:Pseudopodia / Q000502:physiology*; D014795:Visual Pathways / Q000196:embryology*
chemical_list: C570800:CadN protein, Drosophila; D015820:Cadherins; D029721:Drosophila Proteins
keywords: D. melanogaster; brain development; filopodial dynamics; growth cone; live Imaging; neuroscience; synapse formation