Abstract
The high mortality in larval-to-juvenile transition is a big problem in aquaculture which is related to the shifting from endogenous to exogenous feeding. However, the underlying causes remain poorly understood. Autophagy, an evolutionary regulated cellular mechanism, is highly conserved in eukaryotic organisms to maintain energy homeostasis against stress including starvation. To investigate whether autophagy plays a role during larval-to-juvenile transition, we generated atg7 and beclin1 zebrafish mutant lines using CRISPR/Cas9 gene editing technology. In this study, both atg7 and beclin1 null zebrafish died during larval-to-juvenile transition because atg7 and beclin1 mutants were unable to cope with the metabolic stress after yolk absorption and fail to activate autophagy in response to nutrient restriction. Meanwhile, dramatic defects in the intestine architecture and metabolic functions in the liver of these mutants were observed even though refeeding them. Treatment with rapamycin, an activator of autophagy, could effectively extend the survival time of both atg7 and beclin1 null zebrafish through decreasing the metabolic rate while it couldn't activate autophagy in mutants via the canonical pathway. Thus, our results revealed that autophagy played a crucial role in zebrafish ontogeny during larval-to-juvenile transition, and it could be considered as one of the most important endogenous factors judging the survival rate of the developing embryos during this period.
Highlights
On the basis of the developmental events, the transition from the larval to the juvenile stage is crucial during fish ontogeny since embryos shifting from maternal yolk acquisition to extrinsic food resources depending on the cellular metabolism and energy (1)
On the basis of the cell mechanisms, Macroautphagy, a natural regulated pathway disassembles unnecessary or dysfunctional components orchestrated by more than 36 autophagy related-genes conserved from yeast to mammals
Macroautophagy here referred to as autophagy, alters both anabolic and catabolic processes with the help of two key sensors, the activated protein kinase (AMPK), a key energy sensor and the mechanistic target of rapamycin (TOR), a key nutrients sensor(4)
Summary
On the basis of the developmental events, the transition from the larval to the juvenile stage is crucial during fish ontogeny since embryos shifting from maternal yolk acquisition to extrinsic food resources depending on the cellular metabolism and energy (1). Macroautophagy here referred to as autophagy, alters both anabolic and catabolic processes with the help of two key sensors, the activated protein kinase (AMPK), a key energy sensor and the mechanistic target of rapamycin (TOR), a key nutrients sensor(4). Under the nutrient-rich condition, mTOR is activated and stimulates anabolic processes such as gluconeogenesis, protein synthesis, and energy metabolism, whereas catabolic pathway via autophagy is prohibited (6). During starvation stressors mTOR get switched off, thereby enabling the activation of autophagy in wild type zebrafish larvae after maternal yolk depletion at 6 dpf (7, 8). Reactivation of mTOR attenuates autophagy and initiates lysosome regeneration (9)
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