PUBLICATION

Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics

Authors

Fassier, C., Fréal, A., Gasmi, L., Delphin, C., Ten Martin, D., De Gois, S., Tambalo, M., Bosc, C., Mailly, P., Revenu, C., Peris, L., Bolte, S., Schneider-Maunoury, S., Houart, C., Nothias, F., Larcher, J.C., Andrieux, A., Hazan, J.

ID

ZDB-PUB-180315-3

Date

2018

Source

The Journal of cell biology 217(5): 1719-1738 (Journal)

Registered Authors

Hazan, Jamile, Houart, Corinne, Revenu, Celine, Schneider-Maunoury, Sylvie

Keywords

none

MeSH Terms

Locomotion
Motor Neurons/metabolism
Axon Guidance*
Animals
Microtubule-Associated Proteins/metabolism
Adenosine Triphosphatases/chemistry
Adenosine Triphosphatases/metabolism*
Microtubules/metabolism*
Spinal Cord/metabolism
Cytoskeleton/metabolism
Nuclear Proteins/chemistry
Nuclear Proteins/metabolism*
Growth Cones/metabolism
Protein Isoforms/metabolism
Polymerization
Axons/metabolism*
Larva/metabolism
Humans
Gene Knockdown Techniques

(all 19)

PubMed

29535193 Full text @ J. Cell Biol.

Abstract

During neural circuit assembly, extrinsic signals are integrated into changes in growth cone (GC) cytoskeleton underlying axon guidance decisions. Microtubules (MTs) were shown to play an instructive role in GC steering. However, the numerous actors required for MT remodeling during axon navigation and their precise mode of action are far from being deciphered. Using loss- and gain-of-function analyses during zebrafish development, we identify in this study the meiotic clade adenosine triphosphatase Fidgetin-like 1 (Fignl1) as a key GC-enriched MT-interacting protein in motor circuit wiring and larval locomotion. We show that Fignl1 controls GC morphology and behavior at intermediate targets by regulating MT plus end dynamics and growth directionality. We further reveal that alternative translation of Fignl1 transcript is a sophisticated mechanism modulating MT dynamics: a full-length isoform regulates MT plus end-tracking protein binding at plus ends, whereas shorter isoforms promote their depolymerization beneath the cell cortex. Our study thus pinpoints Fignl1 as a multifaceted key player in MT remodeling underlying motor circuit connectivity.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
fignl1	Ab1-fignl1	ml2Tg	control	Prim-5	secondary motor neuron axon	IHC	Fig. 2
fignl1	Ab1-fignl1	ml2Tg	control	Prim-5	secondary motor neuron microtubule	IHC	Fig. 2
fignl1	Ab1-fignl1	WT	control	Long-pec	anterior commissure	IHC	Fig. 1
fignl1	Ab1-fignl1	WT	control	Long-pec	branchiomotor neuron	IHC	Fig. 1
fignl1	Ab1-fignl1	WT	control	Long-pec	cranial nerve II	IHC	Fig. 1
fignl1		WT	control	Prim-25	eye	ISH	Fig. 1
fignl1		WT	control	Prim-15	eye	ISH	Fig. 1
fignl1		WT	control	Bud	head	ISH	Fig. 1
fignl1		WT	control	Prim-5	head	ISH	Fig. 1
fignl1		WT	control	10-13 somites	head	ISH	Fig. 1

1 - 10 of 41

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-fignl1	control	Prim-5	CaP motoneuron axon extension arrested, abnormal	Fig. 3
WT + MO1-fignl1	control	Prim-5	CaP motoneuron axon increased branchiness, abnormal	Fig. 3
WT + MO1-fignl1	control	Prim-5	CaP motoneuron axon truncated, abnormal	Fig. 3
WT + MO1-fignl1	control	Prim-5	Rohon-Beard neuron innervation decreased occurrence, abnormal	Fig. 4
WT + MO1-fignl1	control	Long-pec	hatching decreased occurrence, abnormal	Fig. 3
WT + MO1-fignl1	control	Long-pec	locomotion involved in locomotory behavior decreased process quality, abnormal	Fig. 3
WT + MO1-fignl1	control	Long-pec	locomotion involved in locomotory behavior process quality, abnormal	Fig. 3
WT + MO1-fignl1	control	Long-pec	neuromuscular junction development decreased occurrence, abnormal	Fig. 3
WT + MO1-fignl1	control	Long-pec	secondary motor neuron axon defasciculated, abnormal	Fig. 3
WT + MO1-fignl1	control	Long-pec	secondary motor neuron axon extension arrested, abnormal	Fig. 3

1 - 10 of 15

Show

Mutations / Transgenics

Allele	Construct	Type
ku20Tg	Tg(3xmnx1:GAL4-VP16)	Transgenic Insertion
ml2Tg	Tg(mnx1:GFP)	Transgenic Insertion
rw0Tg	Tg(isl1a:GFP)	Transgenic Insertion
rw021Tg	Tg(atoh7:GFP)	Transgenic Insertion
zf519Tg	Tg(6xUAS:EMTB-3xGFP)	Transgenic Insertion
zf532Tg	Tg(olig2:EGFP)	Transgenic Insertion

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fignl1	MO1-fignl1	MRPHLNO
fignl1	MO2-fignl1	MRPHLNO

Fish

Fish
ml2Tg
ml2Tg + MO1-fignl1
WT
WT + MO1-fignl1

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GFP	EFG	GFP

Mapping

Fassier et al., 2018 ZDB-PUB-180315-3 PMID:29535193

Motor axon navigation relies on Fidgetin-like 1-driven microtubule plus end dynamics

Fassier et al., 2018

ZDB-PUB-180315-3
PMID:29535193