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Title: The role of reactive oxygen species during early embryogenesis of Xenopus laevis
Author: Han, Yue
ISNI:       0000 0004 5919 9480
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2015
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Embryonic development involves a variety of cellular processes, including cell growth, cell proliferation, cell differentiation, cell migration and cell death. The precise regulation of these events is essential for morphogenesis and development. Reactive oxygen species (ROS) have been reported as important second messengers to modulate a variety of proteins and signalling pathways, thereby regulating several cellular processes. Previous studies have shown that fertilisation induces an oxidative burst in sea urchins. However, a role for this fertilisation induced ROS during embryonic development in this system has not been shown. Amphibian embryos, such as those from Xenopus laevis (X. laevis), provide an ideal system to study the role of ROS during embryonic development. We previously established a HyPerYFP line in X. laevis, which permits the visualisation of ROS levels in living oocytes, fertilised eggs and early embryos. Using this line, I showed that fertilisation triggers a dramatic increase in intracellular ROS levels, and this increase in ROS levels is sustained throughout early embryogenesis. Lowering ROS levels using antioxidants (e.g. NAC) impairs mesoderm formation and results in severe developmental defects, which are associated with a down-regulation of several signalling pathways, including PI3K/Akt, TGF-β/Nodal and Wnt/β-catenin signalling. I also showed that the dysregulation of these signalling pathways could be partially rescued by addition of the oxidant H2O2 or the ROS inducer menadione, suggesting that the fertilisation induced ROS helps activate several signalling pathways required for mesoderm formation. Further investigations through loss and gain of function analyses revealed that fertilisation induced calcium wave, which is dependent on IP3, activates ROS production from mitochondria, via the mitochondrial complexes II, III and IV. In addition, treatment of early embryos with mitochondrial inhibitors results in defects in cell division during early embryogenesis. Together, my findings suggest that a sustained high level of ROS is essential for cell cycle progression and the activation of early signalling events, therefore ensuring proper early embryonic development in X. laevis.
Supervisor: Not available Sponsor: Healing Foundation Centre
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available