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A coupled Reaction-Diffusion-Strain model predicts cranial vault formation in development and disease

机译:反应-扩散-应变耦合模型预测颅脑穹ault在发育和疾病中的形成

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摘要

How cells utilize instructions provided by genes and integrate mechanical forces generated by tissue growth to produce morphology is a fundamental question of biology. Dermal bones of the vertebrate cranial vault are formed through the direct differentiation of mesenchymal cells on the neural surface into osteoblasts through intramembranous ossification. Here we join a self-organizing Turing mechanism, computational biomechanics, and experimental data to produce a 3D representative model of the growing cerebral surface, cranial vault bones, and sutures. We show how changes in single parameters regulating signaling during osteoblast differentiation and bone formation may explain cranial vault shape variation in craniofacial disorders. A key result is that toggling a parameter in our model results in closure of a cranial vault suture, an event that occurred during evolution of the cranial vault and that occurs in craniofacial disorders. Our approach provides an initial and important step towards integrating biomechanics into the genotype phenotype map to explain the production of variation in head morphology by developmental mechanisms.
机译:细胞如何利用基因提供的指令并整合组织生长产生的机械力以产生形态是生物学的基本问题。脊椎动物颅穹ault的真皮骨骼是通过膜内骨化作用直接将神经表面的间充质细胞分化为成骨细胞而形成的。在这里,我们加入了自组织图灵机制,计算生物力学和实验数据,以生成生长中的脑表面,颅穹v骨和缝合线的3D代表性模型。我们显示如何在成骨细胞分化和骨形成过程中调节信号的单个参数变化可能解释颅面疾病中颅穹v形状的变化。关键结果是,在我们的模型中切换参数会导致颅穹缝合线关闭,该事件发生在颅穹演变过程中,并且发生在颅面疾病中。我们的方法为将生物力学整合到基因型表型图谱中提供了重要的初始步骤,以解释通过发育机制产生的头部形态变异。

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