The role of inherited determinants and embryonic-extraembryonic cell interactions in models of mammalian embryogenesis
type: CreativeWork
description: Mammalian embryogenesis begins with the fusion of an oocyte and a sperm to create the first cell of the newly developing embryo called the zygote. The mechanisms by which this single cell generates a fully formed organism have long been the subject of study of experimental biologists. Initially, embryonic development is reliant on maternally inherited determinants (e.g., RNA, proteins) generated in the oocyte. Overtime, maternal products are degraded and development is controlled by the zygotic genome. Zygotic genome activation (ZGA) is critical for successful embryogenesis, and yet the precise mechanisms of its regulation remain elusive. The first aim of this thesis was to assess the contribution of inherited cell cycle regulators to the onset of ZGA in the early mouse embryo. Specifically, the role of the maternal cell cycle regulator cyclin B3 was examined through zygote microinjections with mRNA combined with live imaging and pharmacological approaches. The findings presented here show a novel link between cyclin B3 activity and the expression of ZGA-related genes Zscan4, Eif1a and Sp110 in the mouse embryo. Overexpression of a degradation-resistant cyclin B3 resulted in the elongation of the S-phase at the expense of the G2 phase in the 2-cell embryo and a suppression of ZGA-related genes. This effect was partially rescued when embryos were forced through the cell cycle by exposure to a Chk1 inhibitor. Conversely, elongation of the G2 phase through Cdk inhibition resulted in an upregulation of ZGA-related genes, which suggested a close link between the cell cycle progression and ZGA regulation in the early embryo. As embryogenesis proceeds, cells are gradually restricted in potency, and morphogenesis shapes the formation of the tissues and organs in the developing body. Complex signalling interactions between embryonic and extraembryonic tissues are indispensable for successful development. The study of early mammalian post-implantation development is challengi…
abstract: Mammalian embryogenesis begins with the fusion of an oocyte and a sperm to create the first cell of the newly developing embryo called the zygote. The mechanisms by which this single cell generates a fully formed organism have long been the subject of study of experimental biologists. Initially, embryonic development is reliant on maternally inherited determinants (e.g., RNA, proteins) generated in the oocyte. Overtime, maternal products are degraded and development is controlled by the zygotic genome. Zygotic genome activation (ZGA) is critical for successful embryogenesis, and yet the precise mechanisms of its regulation remain elusive. The first aim of this thesis was to assess the contribution of inherited cell cycle regulators to the onset of ZGA in the early mouse embryo. Specifically, the role of the maternal cell cycle regulator cyclin B3 was examined through zygote microinjections with mRNA combined with live imaging and pharmacological approaches. The findings presented here show a novel link between cyclin B3 activity and the expression of ZGA-related genes Zscan4, Eif1a and Sp110 in the mouse embryo. Overexpression of a degradation-resistant cyclin B3 resulted in the elongation of the S-phase at the expense of the G2 phase in the 2-cell embryo and a suppression of ZGA-related genes. This effect was partially rescued when embryos were forced through the cell cycle by exposure to a Chk1 inhibitor. Conversely, elongation of the G2 phase through Cdk inhibition resulted in an upregulation of ZGA-related genes, which suggested a close link between the cell cycle progression and ZGA regulation in the early embryo. As embryogenesis proceeds, cells are gradually restricted in potency, and morphogenesis shapes the formation of the tissues and organs in the developing body. Complex signalling interactions between embryonic and extraembryonic tissues are indispensable for successful development. The study of early mammalian post-implantation development is challengi…
author: Handford, Charlotte Eleni
language: eng
keywords: embryology, gastrulation, neurulation, organogenesis, stem cell differentiation
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-05-31
date modified: 2026-07-22T22:24:31Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.93879