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Title: Programmed cell death during heart development
Author: Sharma, Pundrique Radheyshyam
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2002
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Programmed cell death has been demonstrated to be of importance in mammalian organogenesis. In this thesis, the distribution, regulation and function of programmed cell death are investigated during mouse cardiac septation. During this process, the four chambers and two outflow vessels of the heart become separated from one another. In the mouse, this occurs between embryonic days 10.5 to 13.5. The study commences with a detailed spatio-temporal analysis of programmed cell death during cardiac septation. This demonstrates specific, reproducible foci of apoptotic activity, which are grouped into low intensity and high intensity, the latter occurring in the endocardial cushions as septation completes. This qualitative investigation is then supplemented, and supported, by a quantitative analysis. Immunohistochemical techniques demonstrate which cell types undergo apoptosis during cardiac septation and show that macrophages are not clearing apoptotic debris. The question of an association between cardiac neural crest cells and programmed cell death during the process of septation is addressed using double-labelling for a cardiac neural crest marker, [alpha]-smooth muscle actin, and an apoptosis marker, TUNEL, and by investigation of apoptosis in the Sp2H mutant mouse, in which neural crest cell migration to the cardiac outflow tract is impaired. The results suggest that neural crest cells are involved in apoptosis, and may indeed be dying, within the cardiac outflow tract cushions. The molecular mechanisms that lead to programmed cell death in the heart are then examined, focusing on the death receptor-mediated apoptosis pathway. Evidence is provided that this pathway is involved in programmed cell death during septation. Finally, inhibition of apoptosis in embryo culture is described. Although only preliminary, the results suggest that inhibition of programmed cell death can cause defective development of the interventricular septum.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Physiology