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Dynamic Views of Structure and Function during Heart Morphogenesis


Forouhar, Arian Soroush (2006) Dynamic Views of Structure and Function during Heart Morphogenesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z0X2-HG40.


Congenital heart defects remain the most common birth defect in humans, occurring in over 1% of live births. The high prevalence of cardiac malformations can be partially attributed to limited knowledge regarding the embryonic roots of the disease. A variety of congenital heart defects are thought to arise from combinations of genetic and epigenetic factors. In an effort to better understand this dynamic relationship, our study explores the structure and function of the developing heart and valves and examines hemodynamic factors influencing valvulogenesis. In order to study cardiac mechanics, we employed novel high-speed confocal microscopy and four-dimensional visualization techniques. A dynamic four-dimensional dataset describing heart and valve development along with blood flow patterns throughout cardiac morphogenesis is presented. Utilizing newly developed tools, we propose a novel pumping mechanism in the valveless embryonic heart tube via elastic wave propagation and reflection. We show that this form of pumping leads to oscillatory shear stresses in the developing atrio-ventricular canal, a phenomenon that had not previously been documented. An in vivo method to modulate trans-valvular oscillatory flows is described and used to test our hypothesis that oscillatory shear stress across the primitive valve cushions stimulates heart valve leaflet formation. Our results suggest hemodynamic forces contribute to valvulogenesis and enhance our understanding of normal and abnormal heart valve development.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biological Imaging; Cardiogenesis; Heart Morphogenesis; Heart Tube; Oscillatory Flow; Suction Pump; Zebrafish
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Bioengineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Gharib, Morteza
Thesis Committee:
  • Fraser, Scott E. (chair)
  • Gharib, Morteza (co-chair)
  • Hove, Jay R.
  • Dickinson, Mary E.
  • Dickinson, Michael H.
Defense Date:12 May 2006
Record Number:CaltechETD:etd-06282006-130509
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2757
Deposited By: Imported from ETD-db
Deposited On:12 Jul 2006
Last Modified:09 Aug 2022 17:16

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