Metabolic regulation of the ultradian oscillator Hes1 by reactive oxygen species

Journal of Molecular Biology
Simona VentreDiego di Bernardo

Abstract

Ultradian oscillators are cyclically expressed genes with a period of less than 24h, found in the major signalling pathways. The Notch effector hairy and enhancer of split Hes genes are ultradian oscillators. The physiological signals that synchronise and entrain Hes oscillators remain poorly understood. We investigated whether cellular metabolism modulates Hes1 cyclic expression. We demonstrated that, in mouse myoblasts (C2C12), Hes1 oscillation depends on reactive oxygen species (ROS), which are generated by the mitochondria electron transport chain and by NADPH oxidases NOXs. In vitro, the regulation of Hes1 by ROS occurs via the calcium-mediated signalling. The modulation of Hes1 by ROS was relevant in vivo, since perturbing ROS homeostasis was sufficient to alter Medaka (Oryzias latipes) somitogenesis, a process that is dependent on Hes1 ultradian oscillation during embryo development. Moreover, in a Medaka model for human microphthalmia with linear skin lesions syndrome, in which mitochondrial ROS homeostasis was impaired, we documented important somitogenesis defects and the deregulation of Hes homologues genes involved in somitogenesis. Notably, both molecular and developmental defects were rescued by antioxidant treatm...Continue Reading

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Citations

Jun 2, 2016·Oxidative Medicine and Cellular Longevity·Pierpaola DavalliDomenico D'Arca
May 29, 2016·Cellular and Molecular Life Sciences : CMLS·Sivadasan Bindu DhaneshJackson James
Jun 7, 2016·Scientific Reports·Alessia IndrieriBrunella Franco
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Oct 3, 2018·Development·Hidenobu Miyazawa, Alexander Aulehla
Mar 17, 2019·Biology·Grace H GohDominique Blache
Apr 4, 2021·Cells·Ryan P MendozaJared M Brown

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