Redox stress and signaling during vertebrate embryonic development: Regulation and responses

Abstract

Vertebrate embryonic development requires specific signaling events that regulate cell proliferation and differentiation to occur at the correct place and the correct time in order to build a healthy embryo. Signaling pathways are sensitive to perturbations of the endogenous redox state, and are also susceptible to modulation by reactive species and antioxidant defenses, contributing to a spectrum of passive vs. active effects that can affect redox signaling and redox stress. Here we take a multi-level, integrative approach to discuss the importance of redox status for vertebrate developmental signaling pathways and cell fate decisions, with a focus on glutathione/glutathione disulfide, thioredoxin, and cysteine/cystine redox potentials and the implications for protein function in development. We present a tissue-specific example of the important role that reactive species play in pancreatic development and metabolic regulation. We discuss NFE2L2 (also known as NRF2) and related proteins, their roles in redox signaling, and their regulation of glutathione during development. Finally, we provide examples of xenobiotic compounds that disrupt redox signaling in the context of vertebrate embryonic development. Collectively, this review provides a systems-level perspective on the innate and inducible antioxidant defenses, as well as their roles in maintaining redox balance during chemical exposures that occur in critical windows of development.

Large‐Scale Analysis of Redox‐Sensitive Conditionally Disordered Protein Regions Reveals Their Widespread Nature and Key Roles in High‐Level Eukaryotic Processes

“…Examples of redox‐regulated proteins that rely on conditional disorder are involved in mitochondrial transport and assembly. In mammalians, redox signaling via alteration of redox status of specific protein thiols has been recognized as a major contributor to diverse key processes, such as stem cell proliferation, vertebrate embryonic development, neuronal development, and blood coagulation . Redox regulation is also an emerging theme in cell–cell and cell–extracellular matrix interactions, tying together integrin signaling, angiogenesis, and various diseases.…”

Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

“…Redox signaling is important in developmental processes controlling proliferation, apoptosis, neuronal differentiation and axon formation. The redox status is tightly regulated during development (Marseglia et al, 2014; Timme‐Laragy et al, 2018). Oxidative stress causes synapse loss as a result of impaired mitochondrial function (Mast et al, 2008).…”

Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

“…Examples of redoxregulated proteins that rely on conditional disorder are involved in mitochondrial transport and assembly. In mammalians, redox signaling via alteration of redox status of specific protein thiols has been recognized as a major contributor to diverse key processes, such as stem cell proliferation [85], vertebrate embryonic development [86], neuronal development [87], and blood coagulation [88]. Redox regulation is also an emerging theme in cell-cell and cell-ECM interactions [89], tying together integrin signaling, angiogenesis, and various diseases.…”