PUBLICATION

Zebrafish fin regeneration involves generic and regeneration-specific osteoblast injury responses

Authors

Sehring, I.M., Mohammadi, H.F., Haffner-Luntzer, M., Ignatius, A., Huber-Lang, M., Weidinger, G.

ID

ZDB-PUB-220625-28

Date

2022

Source

eLIFE 11: (Journal)

Registered Authors

Weidinger, Gilbert

Keywords

cell biology, developmental biology, zebrafish

MeSH Terms

Zebrafish Proteins/genetics
Animals
Zebrafish*/genetics
Osteogenesis
Animal Fins/physiology
Osteoblasts
Actomyosin*

(all 7)

PubMed

35748539 Full text @ Elife

Abstract

Successful regeneration requires the coordinated execution of multiple cellular responses to injury. In amputated zebrafish fins, mature osteoblasts dedifferentiate, migrate towards the injury and form proliferative osteogenic blastema cells. We show that osteoblast migration is preceded by cell elongation and alignment along the proximodistal axis, which require actomyosin, but not microtubule turnover. Surprisingly, osteoblast dedifferentiation and migration can be uncoupled. Using pharmacological and genetic interventions, we found that NF-ĸB and retinoic acid signalling regulate dedifferentiation without affecting migration, while the complement system and actomyosin dynamics affect migration but not dedifferentiation. Furthermore, by removing bone at two locations within a fin ray, we established an injury model containing two injury sites. We found that osteoblasts dedifferentiate at and migrate towards both sites, while accumulation of osteogenic progenitor cells and regenerative bone formation only occur at the distal-facing injury. Together, these data indicate that osteoblast dedifferentiation and migration represent generic injury responses that are differentially regulated and can occur independently of each other and of regenerative growth. We conclude that successful fin bone regeneration appears to involve the coordinated execution of generic and regeneration-specific responses of osteoblasts to injury.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bglap	AB	amputation: caudal fin	Adult	regenerating fin	ISH	Fig. 6
c3a.5	hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin	RTPCR	Fig. 5
c5	hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin	RTPCR	Fig. 5
c5ar1	hu4008Tg/hu4008Tg	standard conditions	Adult	caudal fin	ISH	Fig. 5
cyp26b1	AB	amputation: caudal fin	Adult	regenerating fin	ISH	Fig. 6
EGFP	hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin	ISH	Fig. 1
EGFP	hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin	IFL	Fig. 1
Kaede	hu6867Tg/hu6867Tg	ultraviolet light, amputation: caudal fin	Adult	caudal fin osteoblast	IFL	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin c3a.5 expression increased amount, abnormal	Fig. 5
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin c5 expression increased amount, abnormal	Fig. 5
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin EGFP expression decreased amount, abnormal	Fig. 1
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	caudal fin transcriptional attenuation normal process quality, normal	Fig. 1
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	regenerating fin cell division spatial distribution of a process, normal	Fig. 6
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	regenerating fin distal side ossified, abnormal	Fig. 6
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	regenerating fin ossification spatial distribution of a process, abnormal	Fig. 6
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	regenerating fin osteoblast migratory, normal	Fig. 3
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	regenerating fin osteoblast migratory, normal	Fig. 6
hu4008Tg/hu4008Tg	amputation: caudal fin	Adult	regenerating fin osteoblast protruding, normal	Fig. 3

1 - 10 of 32

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Mutations / Transgenics

Allele	Construct	Type
hu4008Tg	Tg1(Ola.Bglap:EGFP)	Transgenic Insertion
hu6867Tg	TgBAC(entpd5a:Kaede)	Transgenic Insertion
tud8Tg	Tg(Ola.Sp7:Cre-ERT2-2A-mCherry)	Transgenic Insertion
tud9Tg	Tg(hsp70l:LOXP-DsRed2-LOXP-NLS-EGFP)	Transgenic Insertion
ulm12Tg	Tg(hsp70l:LOXP-Luciferase-MYC-STOP-LOXP-caHsa.IKBKB-2A-mTagBFP2-V5,cryaa:AmCyan)	Transgenic Insertion
ulm15Tg	Tg(hsp70l:LOXP-Luciferase2-MYC-STOP-LOXP-nYPet-p2A-IkBSR,cryaa:AmCyan)	Transgenic Insertion
zf336Tg	TgBAC(ctsk:Citrine)	Transgenic Insertion

1 - 7 of 7

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
AB
hu4008Tg/hu4008Tg
hu4008Tg/hu4008Tg; hu6867Tg/hu6867Tg
hu6867Tg/hu6867Tg
tud8Tg/tud8Tg
tud9Tg/tud9Tg
ulm12Tg/ulm12Tg
ulm15Tg/ulm15Tg

Antibodies

Name	Type	Isotypes	Host Organism
Ab1-runx2	monoclonal	IgG2b	Mouse
Ab1-sp7	polyclonal	IgG	Rabbit
zns-5	monoclonal	IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
AmCyan	EFG	AmCyan
Citrine	EFG	Citrine
Cre	EFG	Cre
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP
IkBSR	EFG	IkBSR
Kaede	EFG	Kaede
Luciferase	EFG	Luciferase
mCherry	EFG	mCherry
TagBFP	EFG	TagBFP

Mapping

Sehring et al., 2022 ZDB-PUB-220625-28 PMID:35748539

Zebrafish fin regeneration involves generic and regeneration-specific osteoblast injury responses

Sehring et al., 2022

ZDB-PUB-220625-28
PMID:35748539