Maskell, Lauren Jill;
(2019)
Expression and Function of the POU4F2/Brn3b Transcription Factor in the Heart during Development and in Responses to Stress.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Heart morphology, structure and function in the developing and adult heart is tightly controlled by cellular processes including proliferation, differentiation and apoptosis which determine cell fate. Defects in these cellular processes and hence heart development or complications in the adult heart in response to stress can lead to congenital heart disease or cardiovascular disease respectively which cause high rates of mortality globally. The fate of cardiomyocytes during development and in response to stress are highly dependent on changes in gene expression. Hence, factors that control such changes will be important for facilitating cardiac development and hypertrophic responses to stress in the heart. The molecular mechanisms however are not fully understood. The transcription factor (TF) POU4F2/ Brn3b is expressed in cardiomyocytes and regulates several target genes involved in cardiac development. It is highly expressed in the foetal heart and reduced in adult cardiomyocytes, but is re-expressed in response to injury. As such, the role of Brn3b was investigated in the developing heart in more detail by undertaking morphological and molecular analysis of Brn3a KO mouse embryonic hearts. In this study, Brn3b KO mutant mice and wild type (WT) controls were also used to assess the role of this TF in hypertrophic responses induced by Angiotensin II (AngII) infusion (pathological stress) or exercise (physiological stress), by analysing for changes in cardiac morphology, function and genetic changes (parallel studies were also undertaken in cardiomyocyte cultures, e.g. NRVM and H9C2 cells). Functional parameters such as cardiac output, fractional shortening, and ventricular mass, etc. were measured using echocardiography, and histological changes were assessed (e.g. Masson’s trichrome staining) at baseline and 4 weeks post AngII treatment/ exercise. This data showed that cardiac hypertrophy was attenuated in Brn3b KO mice following AngII treatment/ exercise. This suggests that Brn3b may be a novel foetal gene that is required for heart development and for mediating hypertrophic responses following pathological and physiological stress; and may have distinct roles in males and females.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Expression and Function of the POU4F2/Brn3b Transcription Factor in the Heart during Development and in Responses to Stress |
| Event: | UCL |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10066705 |
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