Coordination of development and metabolism in the pre‐midblastula transition zebrafish embryo

Abstract

To define the mechanisms that coordinate early embryonic development and metabolism, we have examined the response of zebrafish embryos to anoxia before the midblastula transition. Our findings reveal that anoxic pre-midblastula transition embryos slow the cell cycle, arrest before the midblastula transition and can recover normally if restored to a normoxic environment. Analyses of respiratory rates reveal that pre-midblastula transition embryos are less reliant on oxidative phosphorylation than older embryos. Interestingly, arrest in anoxia occurs despite inhibition of zygotic transcription, revealing a central role for maternal factors in the response to energy limitation. Consistent with this concept, we demonstrate that the posttranslational energy-sensing AMP-activated protein kinase pathway is activated in anoxia in premidblastula transition embryos. Taken together, these findings demonstrate a maternal program capable of coordinating developmental rate and metabolism in the absence of transcription-based pathways or cell cycle checkpoints.

Spatiotemporal expression and transcriptional regulation of heme oxygenase and biliverdin reductase genes in zebrafish (Danio rerio) suggest novel roles during early developmental periods of heightened oxidative stress

“…During this time period in zebrafish development there is a transition from anoxia tolerance (<24 hpf) to declining survivability due to anoxia sensitivity (~24–48 hpf), with anoxia becoming lethal at approximately 52 hpf (Padilla and Roth, 2001). One explanation for this transition in anoxia sensitivity is the occurrence of a highly coordinated change in metabolism from an anaerobic to an aerobic form of energy production that is more conducive to generating reactive oxygen species (ROS) (Mendelsohn and Gitlin, 2008; Mendelsohn et al, 2008). Furthermore, while GSH recycling typically represents the frontline defense against oxidative stress, oscillating levels of GSH and fluctuations in cytosolic redox environment have been reported between 0–48 hpf in developing zebrafish embryos (Timme-Laragy et al, 2013).…”

Effects of Hydroxylated Polybrominated Diphenyl Ethers in Developing Zebrafish Are Indicative of Disruption of Oxidative Phosphorylation

“…Exposure of zebrafish embryos to OXPHOS disruptors before the midblastula transition (~3–5 hpf) is known to reduce their developmental rate and even arrest their development [19,20]. The 6-OH-BDE47 alters the expression of genes involved in proton transport and carbohydrate metabolism and alters the oxygen consumption of extracted mitochondria in zebrafish which might be a sign of OXPHOS disruption [10].…”

“…Disruption of OXPHOS in fish is also associated with developmental delay [19,20]. Zebrafish embryos reduce their developmental rate and even arrest their development when exposed to OXPHOS disruptors before the stage of midblastula transition [19].…”

“…Zebrafish embryos reduce their developmental rate and even arrest their development when exposed to OXPHOS disruptors before the stage of midblastula transition [19]. Lai et al [20] screened 12,000 natural products on effects on early zebrafish development.…”

Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease

“…Throughout the first 5 days of zebrafish development, the embryo consumes the presumptive equivalent of a high-protein diet in mammals by absorbing BCAA-containing proteins from the yolk (Link et al, 2006; Tay et al, 2006). During the earliest stages of development, within the first few hours post-fertilization, the metabolic needs of the embryo are largely met by maternally derived mitochondria and mRNA (Mendelsohn and Gitlin, 2008; Zhang et al, 2008; Abrams and Mullins, 2009). However, as embryogenesis proceeds, BCAA metabolism increasingly relies upon zygotic transcription.…”