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Elife. 2015 Jun 15;4. doi: 10.7554/eLife.05061.

Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3.

Author information

1
Institut Curie, Centre de Recherche, Paris, France.
2
Department of Physiology, University of California San Francisco, San Francisco, United States.
3
Muséum National d'Histoire naturelle, Inserm U 1154, CNRS, UMR 7196, Muséum National d'Histoire Naturelle, Paris, France.
4
Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 6, Paris, France.
5
Neural Circuits and Behaviour Group, Uni Research AS High Technology Centre, Bergen, Norway.
6
Division of Molecular and Developmental Biology, National Institute of Genetics, Shizuoka, Japan.
7
Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.

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.

KEYWORDS:

axonal development; neuroscience; neurotrophic signaling; visual system; zebrafish

PMID:
26076409
PMCID:
PMC4467164
DOI:
10.7554/eLife.05061
[Indexed for MEDLINE]
Free PMC Article

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