| RRC ID |
40022
|
| Author |
Auer TO, Xiao T, Bercier V, Gebhardt C, Duroure K, Concordet JP, Wyart C, Suster M, Kawakami K, Wittbrodt J, Baier H, Del Bene F.
|
| Title |
Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3.
|
| Journal |
Elife
|
| 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.
|
| Volume |
4
|
| Published |
2015-6-15
|
| DOI |
10.7554/eLife.05061
|
| PMID |
26076409
|
| PMC |
PMC4467164
|
| MeSH |
Animals
Animals, Genetically Modified
Axons / physiology*
Biological Transport / physiology
Blotting, Western
Cell Polarity / physiology*
Chromosome Mapping
Cloning, Molecular
DNA Primers / genetics
Genotype
Immunohistochemistry
In Situ Hybridization
Kinesins / genetics
Kinesins / metabolism*
Microscopy, Confocal
Microscopy, Electron, Transmission
Mitochondria / metabolism
Neurogenesis / physiology*
Neurotrophin 3 / metabolism*
Real-Time Polymerase Chain Reaction
Signal Transduction / physiology*
Time-Lapse Imaging
Zebrafish / embryology*
Zebrafish Proteins / metabolism*
|
| IF |
7.08
|
| Times Cited |
19
|
|
WOS Category
|
BIOLOGY
|
| Resource |
| Zebrafish |
gSA2AzGFF49A |
