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Investigating the role of Setd5 in cardiac development

Cheung, Michelle Yu-Qing; (2021) Investigating the role of Setd5 in cardiac development. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

There are several genes required for cardiac development and perturbations in intricate gene regulatory networks may lead to cardiac defects. Haploinsufficiency of TBX1 leads to human 22q11 deletion syndrome (22q11DS) which is characterised by a range of defects including cardiovascular malformations. Mouse models partially recapitulate some of the defects observed. The online browser “Deciphering the Mechanisms of Developmental Disorders” (DMDD) was used to screen for genes that resulted in a cardiovascular phenotype similar to that caused by Tbx1 haploinsufficiency. This identified Setd5 as a potentially important gene for further study. The data presented by the browser led to the interpretation that Setd5 is required for embryonic development and its deletion is lethal. Heterozygous embryos presented with defects including common arterial trunk (CAT), double outlet right ventricle (DORV) and ventricular septal defect (VSD). Because of the partial overlap between the defects caused when Setd5 is haploinsufficient and when Tbx1 is haploinsufficient, this led to the investigation of a potential genetic interaction between Setd5 and Tbx1. The Setd5 heterozygous phenotype was delineated, but work in this thesis revealed no genetic interaction between the two genes of interest. The embryonic lethality of constitutive Setd5 null embryos limits the full analysis into the role of Setd5 in cardiac development. Conditional deletion of Setd5 in the cardiopharyngeal mesoderm revealed an important role of Setd5 in the development of the outflow tract and cardiac chambers. Moreover, the expression of specific cardiac-specific genes was disrupted. The work in this thesis reveals a previously unreported role of Setd5 in cardiac development, including the cardiac defects and differential expression of some cardiac-specific genes observed when Setd5 is deleted in the cardiopharyngeal mesoderm.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating the role of Setd5 in cardiac development
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2021. 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
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10119369
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