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Title: Emergence of cardiac function and cell types during early embryogenesis
Author: Miranda, Antonio M. A.
ISNI:       0000 0004 7229 5602
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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The heart is the first organ to form and function during embryonic development. Over the past few years, research on cardiac development has focused on uncovering the genetic mechanism controlling cardiac differentiation and clarifying the embryonic origin of the different cardiac lineages. The study of the physiological mechanisms behind cardiac function has proven instrumental for our understanding of heart disease and the interplay between different cardiac cells. However, there is not an extensive body of literature on the role of physiology on early embryonic development, especially on cardiac development. In this thesis, I present my work on the early stages of heart development, focusing on the events occurring from the formation of the cardiac crescent to the linear heart tube stage. This thesis is divided in 3 result chapters. In the first result chapter (chapter 3), I present the methods I developed to perform live imaging of mouse embryos, including calcium imaging, and to extract quantitative information. On the second result chapter (chapter 4), I described the work I performed investigating the physiological mechanisms of early heart development, their role in cardiac differentiation, and a detailed single-cell RNA sequencing analysis of early heart development. On the last result chapter (chapter 5), I explore preliminary data on a potential contribution of endodermal cells to the formation of the heart. The work presented here has led to the discovery of Spontaneous Asynchronous Calcium Oscillations (SACOs) in the early cardiac mesoderm and a key role for NCX1 in regulating these oscillations and cardiac differentiation. Single-cell RNA sequencing analysis suggests a potential role for Naca and Fbxo32 in regulating early cardiac function. I have also identified potential new markers for both the First and Second Heart Field. Lastly, I found evidence that the endoderm may be contributing to the Second Heart Field, although the function of these cells is still unclear.
Supervisor: Srinivas, Shankar Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available