PUBLICATION
Zebrafish raptor mutation inhibits the activity of mTORC1, inducing craniofacial defects due to autophagy-induced neural crest cell death
- Authors
- Tucker, S.K., Gosul, R., Swartz, M.E., Zhang, S., Eberhart, J.K.
- ID
- ZDB-PUB-240322-2
- Date
- 2024
- Source
- Development (Cambridge, England) 151(6): (Journal)
- Registered Authors
- Eberhart, Johann, Swartz, Mary
- Keywords
- Autophagy, Cell death, Craniofacial, MTOR, Neural crest, Zebrafish
- MeSH Terms
-
- Animals
- Autophagy/genetics
- Cell Death
- Mechanistic Target of Rapamycin Complex 1/metabolism
- Mutation/genetics
- Neural Crest*/metabolism
- Regulatory-Associated Protein of mTOR/genetics
- Regulatory-Associated Protein of mTOR/metabolism
- Signal Transduction/genetics
- TOR Serine-Threonine Kinases/genetics
- TOR Serine-Threonine Kinases/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 38512806 Full text @ Development
Citation
Tucker, S.K., Gosul, R., Swartz, M.E., Zhang, S., Eberhart, J.K. (2024) Zebrafish raptor mutation inhibits the activity of mTORC1, inducing craniofacial defects due to autophagy-induced neural crest cell death. Development (Cambridge, England). 151(6):.
Abstract
The mechanistic target of rapamycin (mTOR) coordinates metabolism and cell growth with environmental inputs. mTOR forms two functional complexes: mTORC1 and mTORC2. Proper development requires both complexes but mTORC1 has unique roles in numerous cellular processes, including cell growth, survival and autophagy. Here, we investigate the function of mTORC1 in craniofacial development. We created a zebrafish raptor mutant via CRISPR/Cas9, to specifically disrupt mTORC1. The entire craniofacial skeleton and eyes were reduced in size in mutants; however, overall body length and developmental timing were not affected. The craniofacial phenotype associates with decreased chondrocyte size and increased neural crest cell death. We found that autophagy is elevated in raptor mutants. Chemical inhibition of autophagy reduced cell death and improved craniofacial phenotypes in raptor mutants. Genetic inhibition of autophagy, via mutation of the autophagy gene atg7, improved facial phenotypes in atg7;raptor double mutants, relative to raptor single mutants. We conclude that finely regulated levels of autophagy, via mTORC1, are crucial for craniofacial development.
Errata / Notes
This article is corrected by ZDB-PUB-240429-14.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping