Role of Mechanical Forces in Cardiac C-Looping.

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DESCRIPTION (provided by applicant): During cardiac C-looping, which is an important morphogenetic phase in heart development, the primitive heart tube bends ventrally and rotates to the right. Abnormal looping leads to serious congenital birth defects and the exact reasons behind looping are not fully known. Recent work in our lab has identified biomechanical forces responsible for C-looping. To completely understand the biophysical mechanisms of looping, however, the distributions of these forces need to be identified. This is the primary aim of this truly interdisciplinary project. Data (stresses, strains, gross shape changes) from computational and experimental models are compared to arrive at the correct distribution of biomechanical forces. Since the development of the chicken heart is very similar to that of the human heart, the chick embryo is used as the experimental model. The finite element technique is used to develop the computational model. Although rapid progress is being made in identifying the genetic factors responsible for looping, the mechanisms of gene action remain poorly understood. The proposed research can help interpret results from experiments involving genetic manipulations currently being performed in research laboratories elsewhere.