WNT signalling in the patterning of human gastruloids
type: CreativeWork
description: The study of early human development poses a challenge due to technical and ethical limitations, particularly during the initial four weeks following fertilisation. During this critical period, the fundamental aspects of the body plan are established through a process known as gastrulation, which begins 14 days post fertilisation. Because of the 14-day rule imposed on human embryo research, no experimental studies have been conducted beyond this date. The derivation of human embryonic stem cells (hESCs) has opened up numerous opportunities for studying early cell fate decisions and signals involved in this process. In particular, these cells have enabled the development of embryo models that allow the exploration of various aspects of early development. One of these models is the ‘gastruloid’ which results from the aggregation of small numbers of hESCs and leads to the formation of the body plan. WNT signalling, an evolutionary conserved pathway, is known to play a crucial role during gastrulation with its dysregulation leading to various developmental abnormalities and diseases. This thesis examines the role of WNT signalling in the patterning of human gastruloids. By applying different concentrations of WNT agonists, it is shown that the levels of WNT signalling affect cell differentiation as well as elongation and morphology of the gastruloids. Higher WNT levels induce Brachyury expression, whereas lower favour SOX17 expression, triggering the morphogenesis of SOX17+ tube-like structures. Through these experiments, it is further revealed that human gastruloids might recapitulate the mode of endoderm specification recently observed in mouse embryos. Additionally, this thesis indicates that specifically non-canonical WNT signalling affects the elongation of gastruloids. These responses highlight the high sensitivity of the system to the signalling environment. In addition to WNT signalling, BMP and NODAL also act as critical molecular pathways during gastrulation. …
abstract: The study of early human development poses a challenge due to technical and ethical limitations, particularly during the initial four weeks following fertilisation. During this critical period, the fundamental aspects of the body plan are established through a process known as gastrulation, which begins 14 days post fertilisation. Because of the 14-day rule imposed on human embryo research, no experimental studies have been conducted beyond this date. The derivation of human embryonic stem cells (hESCs) has opened up numerous opportunities for studying early cell fate decisions and signals involved in this process. In particular, these cells have enabled the development of embryo models that allow the exploration of various aspects of early development. One of these models is the ‘gastruloid’ which results from the aggregation of small numbers of hESCs and leads to the formation of the body plan. WNT signalling, an evolutionary conserved pathway, is known to play a crucial role during gastrulation with its dysregulation leading to various developmental abnormalities and diseases. This thesis examines the role of WNT signalling in the patterning of human gastruloids. By applying different concentrations of WNT agonists, it is shown that the levels of WNT signalling affect cell differentiation as well as elongation and morphology of the gastruloids. Higher WNT levels induce Brachyury expression, whereas lower favour SOX17 expression, triggering the morphogenesis of SOX17+ tube-like structures. Through these experiments, it is further revealed that human gastruloids might recapitulate the mode of endoderm specification recently observed in mouse embryos. Additionally, this thesis indicates that specifically non-canonical WNT signalling affects the elongation of gastruloids. These responses highlight the high sensitivity of the system to the signalling environment. In addition to WNT signalling, BMP and NODAL also act as critical molecular pathways during gastrulation. …
author: Mantziou, Veronika
language: eng
keywords: Developmental biology, Embryology, Human gastrulation, Human gastruloids, Stem cell models, Teratogenicity
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/cf6c4826-6acc-475e-a3f0-f5104e140308/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-09-30
date modified: 2026-07-22T22:24:04Z
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.107564