PUBLICATION

Autophagy coordinates chondrocyte development and early joint formation in zebrafish

Authors

Moss, J.J., Wirth, M., Tooze, S.A., Lane, J.D., Hammond, C.L.

ID

ZDB-PUB-211029-5

Date

2021

Source

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35: e22002 (Journal)

Registered Authors

Hammond, Chrissy, Tooze, Sharon

Keywords

Atg13, autophagy, chondrocytes, joints, zebrafish

MeSH Terms

Autophagy
Animals
Cell Differentiation
Chondrogenesis*
Chondrocytes/cytology*
Joints/embryology*
Autophagy-Related Proteins/metabolism*
Zebrafish/embryology*

(all 8)

PubMed

34708458 Full text @ FASEB J.

Abstract

Autophagy is a catabolic process responsible for the removal of waste and damaged cellular components by lysosomal degradation. It plays a key role in fundamental cell processes, including ER stress mitigation, control of cell metabolism, and cell differentiation and proliferation, all of which are essential for cartilage cell (chondrocyte) development and survival, and for the formation of cartilage. Correspondingly, autophagy dysregulation has been implicated in several skeletal disorders such as osteoarthritis and osteoporosis. To test the requirement for autophagy during skeletal development in zebrafish, we generated an atg13 CRISPR knockout zebrafish line. This line showed a complete loss of atg13 expression, and restricted autophagic activity in vivo. In the absence of autophagy, chondrocyte maturation was accelerated, with chondrocytes exhibiting signs of premature hypertrophy. Focussing on the jaw element, autophagy disruption affected joint articulation causing restricted mouth opening. This gross behavioural phenotype corresponded with a failure to thrive, and death in homozygote atg13 nulls within 17 days. Taken together, our results are consistent with autophagy contributing to the timely regulation of chondrocyte maturation and for extracellular matrix formation.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: bafilomycin A1	Day 5	chondrocyte amphisome amount, normal	Fig. 7
WT	chemical treatment by environment: bafilomycin A1	Day 5	chondrocyte autophagosome amount, normal	Fig. 7
WT	chemical treatment by environment: bafilomycin A1	Day 5	chondrocyte exocytic vesicle decreased amount, abnormal	Fig. 7
atg13^fci500/+	standard conditions	Prim-5	whole organism normal length, normal	Fig. 1
atg13^fci500/+	standard conditions	Long-pec	whole organism normal length, normal	Fig. 1
atg13^fci500/+	standard conditions	Protruding-mouth	whole organism normal length, normal	Fig. 1
atg13^fci500/+	standard conditions	Day 5	swim bladder inflated, normal	Fig. 1
atg13^fci500/+	standard conditions	Day 5	trunk straight, normal	Fig. 1
atg13^fci500/+	standard conditions	Day 5	whole organism normal length, normal	Fig. 1
atg13^fci500/+	standard conditions	Day 5	whole organism viable, normal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fci500		Small Deletion	atg13
hu5910Tg	TgBAC(col2a1a:mCherry)	Transgenic Insertion
zf155Tg	Tg(CMV:EGFP-map1lc3b)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
atg13	CRISPR1-atg13	CRISPR

Fish

Fish
atg13^{fci500/fci500}
atg13^{fci500/fci500}; hu5910Tg
atg13^{fci500/fci500}; zf155Tg
atg13^fci500/+
hu5910Tg
WT
zf155Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
mCherry	EFG	mCherry

Mapping

Moss et al., 2021 ZDB-PUB-211029-5 PMID:34708458

Autophagy coordinates chondrocyte development and early joint formation in zebrafish

Moss et al., 2021

ZDB-PUB-211029-5
PMID:34708458