PUBLICATION

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

Authors

Auer, T.O., Xiao, T., Bercier, V., Gebhardt, C., Duroure, K., Concordet, J.P., Wyart, C., Suster, M., Kawakami, K., Wittbrodt, J., Baier, H., Del Bene, F.

ID

ZDB-PUB-150616-2

Date

2015

Source

eLIFE 4: (Journal)

Registered Authors

Auer, Thomas, Baier, Herwig, Bercier, Valérie, Del Bene, Filippo, Duroure, Karine, Gebhardt, Christoph, Kawakami, Koichi, Suster, Maximiliano, Wittbrodt, Jochen, Wyart, Claire, Xiao, Tong

Keywords

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

MeSH Terms

Axons/physiology*
Blotting, Western
Animals, Genetically Modified
Mitochondria/metabolism
Biological Transport/physiology
Neurogenesis/physiology*
Microscopy, Electron, Transmission
Microscopy, Confocal
Chromosome Mapping
Zebrafish/embryology*
Zebrafish Proteins/metabolism*
Real-Time Polymerase Chain Reaction
Kinesins/genetics
Kinesins/metabolism*
Time-Lapse Imaging
Cloning, Molecular
Cell Polarity/physiology*
Genotype
DNA Primers/genetics
Animals
Neurotrophin 3/metabolism*
Signal Transduction/physiology*
In Situ Hybridization
Immunohistochemistry

(all 24)

PubMed

26076409 Full text @ 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.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
alcama	zn-5	kif5aa^{ic3023/ic3023}	standard conditions	Long-pec	cranial nerve II	IHC	Fig. 2
alcama	zn-5	kif5aa^{ic3023/ic3023}	standard conditions	Long-pec	retinal ganglion cell axon	IHC	Fig. 2
alcama	zn-5	kif5aa^{ic3024/ic3024}	standard conditions	Long-pec	cranial nerve II	IHC	Fig. 2
alcama	zn-5	kif5aa^{ic3024/ic3024}	standard conditions	Long-pec	retinal ganglion cell axon	IHC	Fig. 2
alcama	zn-5	WT	standard conditions	Long-pec	cranial nerve II	IHC	Fig. 2
alcama	zn-5	WT	standard conditions	Long-pec	retinal ganglion cell axon	IHC	Fig. 2
bdnf		kif5aa^{ic3023/ic3023}	standard conditions	Day 4	whole organism	RTPCR	Fig. 6
bdnf		kif5aa^{ic3024/ic3024}	standard conditions	Day 4	whole organism	RTPCR	Fig. 6
bdnf		WT	standard conditions	Day 4	whole organism	RTPCR	Fig. 6
GCaMP		a4598Tg	standard conditions	Day 5 to Days 7-13	optic tectum dendrite	IFL	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
atoh7^th241/th241	standard conditions	Day 4	whole organism ntf3 expression increased amount, abnormal	Fig. 6
kif5aa^{ic3023/ic3023}	standard conditions	Prim-5	brain kif5aa expression decreased amount, abnormal	Fig. 1
kif5aa^{ic3023/ic3023}	standard conditions	Long-pec	optic chiasma development process quality, normal	Fig. 2
kif5aa^{ic3023/ic3023}	standard conditions	Long-pec	optic nerve morphogenesis process quality, normal	Fig. 2
kif5aa^{ic3023/ic3023}	standard conditions	Long-pec	retinal ganglion cell axon guidance process quality, normal	Fig. 2
kif5aa^{ic3023/ic3023}	standard conditions	Protruding-mouth	brain kif5aa expression decreased amount, abnormal	Fig. 1
kif5aa^{ic3023/ic3023}	standard conditions	Protruding-mouth	retinal ganglion cell layer kif5aa expression decreased amount, abnormal	Fig. 1
kif5aa^{ic3023/ic3023}	standard conditions	Day 4	optic tectum ntf3 expression increased amount, abnormal	Fig. 6
kif5aa^{ic3023/ic3023}	standard conditions	Day 4	optic tectum ntf3 expression increased distribution, abnormal	Fig. 6
kif5aa^{ic3023/ic3023}	standard conditions	Day 4	whole organism kif5aa expression decreased amount, abnormal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
a4598Tg	Tg(elavl3:GCaMP5G)	Transgenic Insertion
ic3021Tg	Tg(UAS:sypb-GFP)	Transgenic Insertion
ic3023		Small Deletion	kif5aa
ic3024		Small Deletion	kif5aa
ic3025Tg	Tg(isl2b:GAL4,myl7:EGFP)	Transgenic Insertion
icm21Tg	Tg(UAS:BoTxBLC-GFP)	Transgenic Insertion
nkgsa2azgff49aGt	Gt(gSA2Az-GAL4FF)	Transgenic Insertion
s311tTg	Tg(pou4f3:GAL4)	Transgenic Insertion
s318tTg	Tg(pou4f3:GAL4,UAS:GAP-GFP)	Transgenic Insertion
s356tTg	Tg(pou4f3:GAP-GFP)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
kif5aa	TALEN1-kif5aa	TALEN

Fish

Fish
a4598Tg
atoh7^th241/th241
ic3021Tg; ic3025Tg
ic3021Tg; ic3025Tg; tpl2Tg
ic3025Tg
ic3025Tg; tpl2Tg
ic3025Tg; zf350Tg
kif5aa^{ic3023/ic3023}
kif5aa^{ic3023/ic3023}; a4598Tg
kif5aa^{ic3023/ic3023}; ic3021Tg; ic3025Tg

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Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-ntf3	polyclonal	ntf3	IgG	Rabbit
Ab1-pvalb	monoclonal		IgG1	Mouse
Ab2-prkcb	polyclonal			Rabbit
zn-5	monoclonal	alcama	IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
BoTxBLC	EFG	BoTxBLC
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GAL4FF	EFG	GAL4FF
GCaMP	EFG	GCaMP
GFP	EFG	GFP
mRFP	EFG	mRFP

Mapping

Auer et al., 2015 ZDB-PUB-150616-2 PMID:26076409

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

Auer et al., 2015

ZDB-PUB-150616-2
PMID:26076409