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
-
- Animals
- Autophagy
- Autophagy-Related Proteins/metabolism*
- Cell Differentiation
- Chondrocytes/cytology*
- Chondrogenesis*
- Joints/embryology*
- Zebrafish/embryology*
- PubMed
- 34708458 Full text @ FASEB J.
Citation
Moss, J.J., Wirth, M., Tooze, S.A., Lane, J.D., Hammond, C.L. (2021) Autophagy coordinates chondrocyte development and early joint formation in zebrafish. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 35:e22002.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping