Role of Mechanical Forces in Cardiac C-Looping.

描述(由申请人提供)： 心脏C-环是心脏发育的一个重要的形态发生阶段，在此过程中，原始的心管向右弯曲和旋转。异常环路会导致严重的先天性出生缺陷，而环路背后的确切原因尚不完全清楚。我们实验室最近的工作已经确定了导致C-环的生物力学因素。然而，为了完全理解环路的生物物理机制，需要确定这些力的分布。这是这个真正跨学科项目的主要目标。将计算模型和实验模型的数据(应力、应变、总体形状变化)进行比较，以得出生物机械力的正确分布。由于鸡心的发育与人的心脏非常相似，因此采用鸡胚胎作为实验模型。利用有限元技术建立了计算模型。尽管在识别导致循环的遗传因素方面取得了快速进展，但对基因作用的机制仍知之甚少。这项拟议的研究可以帮助解释目前在其他研究实验室进行的涉及基因操作的实验结果。

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.