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Title: A study of the control of early cardiac morphogenesis in Xenopus laevis
Author: Breckenridge, R. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2001
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The heart develops from a linear tubular precursor, which loops to the right and undergoes terminal differentiation to form the multi-chambered heart. Heart looping is the earliest manifestation of left-right asymmetry, and determines the eventual heart situs. The signalling processes that impart laterality to the unlooped heart tube are poorly understood. Bone Morphogenetic Protein 4 (BMP4) signalling has been shown to be important at a number of points in heart development. Genetic examination of zebrafish development has shown that BMP4 expression, normally left sided, is perturbed in mutants with altered direction of heart looping and situs. This project seeks to elucidate the control of heart looping by BMP4 by studying possible upstream and downstream factors in a putative cascade regulating heart looping, and the effects of BMP4 misexpression on the heart tube itself. I have shown that, in common with zebrafish, BMP4 is expressed predominantly on the left of the Xenopus linear heart tube. I also demonstrate that ectopic expression of nodal RNA upregulates BMP4 expression, linking asymmetric BMP4 expression to the left-right axis. I have used the Xenopus laevis transgenic methodology to manipulate the BMP4 pathway during heart looping morphogenesis, and show that transgenic embryos overexpressing BMP4 bilaterally in the heart tube demonstrate randomised heart situs, whereby inhibiting BMP4 signalling by expressing noggin or a truncated, dominant negative BMP4 receptor prevents heart looping. Hence, BMP4 signalling imparts laterality to the heart tube in Xenopus and is also required for the looping process to occur. This BMP4-dependent looping process appears to be independent of chamber formation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available