PUBLICATION

Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish

Authors

Holmgren, M., Ravicz, M.E., Hancock, K.E., Strelkova, O., Kallogjeri, D., Indzhykulian, A.A., Warchol, M.E., Sheets, L.

ID

ZDB-PUB-211022-33

Date

2021

Source

eLIFE 10: (Journal)

Registered Authors

Sheets, Lavinia

Keywords

neuroscience, zebrafish

MeSH Terms

Animals
Biomechanical Phenomena
Hair Cells, Auditory/physiology
Lateral Line System/injuries*
Lateral Line System/physiology
Mechanoreceptors/physiology*
Mechanotransduction, Cellular*
Synapses/physiology*
Zebrafish/injuries*
Zebrafish/physiology

(all 10)

PubMed

34665127 Full text @ Elife

Abstract

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.

Genes / Markers

Marker	Marker Type	Name
actb1	GENE	actin, beta 1
lhfpl5b	GENE	LHFPL tetraspan subfamily member 5b
tnks1bp1	GENE	tankyrase 1 binding protein 1

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	mechanical stress	Days 7-13	lateral line morphology, normal	Figure 2
AB	mechanical stress	Days 7-13	lateral line normal position, normal	Figure 2
AB	mechanical stress	Days 7-13	neuromast hair cell Ab6-pvalb labeling spatial pattern, abnormal	Figure 4
AB	mechanical stress	Days 7-13	neuromast hair cell Ab6-pvalb labeling spatial pattern, abnormal	Figure 2
AB	mechanical stress	Days 7-13	neuromast hair cell cell division normal frequency, normal	Figure 11.
AB	mechanical stress	Days 7-13	neuromast hair cell innervation process quality, normal	Figure 7
AB	mechanical stress	Days 7-13	neuromast hair cell kinocilium disorganized, abnormal	Figure 9
AB	mechanical stress	Days 7-13	neuromast hair cell kinocilium swollen, abnormal	Figure 9
AB	mechanical stress	Days 7-13	neuromast hair cell postsynaptic density ab1-pan-maguk labeling decreased amount, abnormal	Figure 4
AB	mechanical stress	Days 7-13	neuromast hair cell postsynaptic density ab1-pan-maguk labeling spatial pattern, abnormal	Figure 5.

1 - 10 of 29

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
nl1Tg	TgBAC(neurod1:EGFP)	Transgenic Insertion
vo8Tg	Tg(myo6b:actb1-EGFP,myl7:EGFP)	Transgenic Insertion
vo35		Small Deletion	lhfpl5b
w200Tg	Tg(mpeg1:YFP)	Transgenic Insertion
y229Gt	Gt(T2KSAG)	Transgenic Insertion	tnks1bp1

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
AB
lhfpl5b^vo35/vo35
nl1Tg/nl1Tg
w200Tg/w200Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
YFP	EFG	YFP

Mapping

Holmgren et al., 2021 ZDB-PUB-211022-33 PMID:34665127

Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish

Holmgren et al., 2021

ZDB-PUB-211022-33
PMID:34665127