The Investigation of Signalling Pathways Governing Cardiac Progenitor Cell Migration

Stephenson, Sophie (2024) The Investigation of Signalling Pathways Governing Cardiac Progenitor Cell Migration. Doctoral thesis, University of East Anglia.

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Abstract

Cellular migration is achieved through the production of cellular protrusions that respond to extra-cellular signals through receptor detection enabling the movement of the cell in a particular direction. Cardiac progenitor cells (CPCs) undergo long range migration in early embryogenesis to enable correct formation of the primitive heart tube in a process known as cardiogenesis. This involves their ingression through the primitive streak during gastrulation and subsequent migration to the anterior of the embryo. Cellular signals that guide CPCs during this process are widely unknown and an intricate pathway involving interactions amongst these signals is yet to be deciphered. Achieving this enables advances in stem cell therapies for patients to allow repair of injured myocardium and identification of genes associated with cardiac malformations in humans allowing appropriate genetic screening.

Preliminary studies revealed an upregulation of Follistatin (FST) by previously identified genes; BMP2, Wnt3a and Smad1-EVE that had a role in controlling CPC migration. The main question this thesis aims to address is FST’ role within cardiogenesis and its’ subsequent interactions with these latter signals to control CPC migration. An analysis method was developed to study this. This involved live imaging of CPCs in real-time embryo development and adaptations to the subsequent analysis approach to show CPC migration parameters. Through this method, rescue experiments could be conducted which discovered interactions between BMP2, Wnt3a and Smad1-EVE with FST within a negative feedback loop. It is later predicted that BMP2 receptor under- or over-sensitisation of the extracellular BMP2 gradient that CPCs are documented to be exposed to within their migration is achieved during FST upregulation or knockdown through the inhibitory relationship between FST and BMP2. This could be hypothesized and linked to the formation of cellular protrusions documented to be through PI3K stabilisation explaining CPC directionality predicted to be causative of found migration parameters.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	11 Jun 2025 08:45
Last Modified:	11 Jun 2025 08:45
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99441
DOI:

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