title: Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3.
abstract: Development and function of highly polarized cells such as neurons depend on microtubule-associated intracellular transport, but little is known about contributions of specific molecular motors to the establishment of synaptic connections. In this study, we investigated the function of the Kinesin I heavy chain Kif5aa during retinotectal circuit formation in zebrafish. Targeted disruption of Kif5aa does not affect retinal ganglion cell differentiation, and retinal axons reach their topographically correct targets in the tectum, albeit with a delay. In vivo dynamic imaging showed that anterograde transport of mitochondria is impaired, as is synaptic transmission. Strikingly, disruption of presynaptic activity elicits upregulation of Neurotrophin-3 (Ntf3) in postsynaptic tectal cells. This in turn promotes exuberant branching of retinal axons by signaling through the TrkC receptor (Ntrk3). Thus, our study has uncovered an activity-dependent, retrograde signaling pathway that homeostatically controls axonal branching.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Auer
authors.affiliation: Department of Physiology, University of California San Francisco, San Francisco, United States.
authors.forename: Tong
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Bercier
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Duroure
authors.affiliation: Muséum National d'Histoire naturelle, Inserm U 1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Concordet
authors.affiliation: Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 6, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Wyart
authors.affiliation: Neural Circuits and Behaviour Group, Uni Research AS High Technology Centre, Bergen, Norway.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Suster
authors.affiliation: Division of Molecular and Developmental Biology, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.
authors.forename: Joachim
authors.identifier: http://orcid.org/0000-0001-8550-7377
authors.initials: J
authors.lastname: Wittbrodt
authors.affiliation: Department of Physiology, University of California San Francisco, San Francisco, United States.
authors.forename: Herwig
authors.initials: H
authors.lastname: Baier
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Filippo
authors.identifier: http://orcid.org/0000-0001-8551-2846
authors.initials: F
authors.lastname: Del Bene
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D016764:Cell Polarity / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D020933:Neurotrophin 3; D029961:Zebrafish Proteins; C000605630:Kif5aa protein, zebrafish; D016547:Kinesins
keywords: axonal development; neuroscience; neurotrophic signaling; visual system; zebrafish