生物
斑马鱼
自噬
mTORC1型
细胞生物学
程序性细胞死亡
颅面
突变体
吗啉
TOR信号
遗传学
细胞凋亡
基因
信号转导
PI3K/AKT/mTOR通路
作者
Scott K. Tucker,Ritika Gosul,Mary E. Swartz,Stephanie Zhang,Johann K. Eberhart
出处
期刊:Development
[The Company of Biologists]
日期:2024-03-15
卷期号:151 (6)
摘要
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.
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