Department of Mechanical Engineering, Pennsylvania State University, 341 Leonhard Building, University Park, PA, 16802, USA.
Department of Anthropology, Pennsylvania State University, 409 Carpenter Building, University Park, PA, 16802, USA.
Biomech Model Mechanobiol. 2019 Aug;18(4):1197-1211. doi: 10.1007/s10237-019-01139-z. Epub 2019 Apr 20.
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 toward integrating biomechanics into the genotype phenotype map to explain the production of variation in head morphology by developmental mechanisms.
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来产生形态，这是生物学的一个基本问题。脊椎动物颅顶的真皮骨是通过间质细胞在神经表面通过膜内成骨直接分化为成骨细胞形成的。在这里，我们将自组织图灵机制、计算生物力学和实验数据结合起来，生成一个不断生长的大脑表面、颅顶骨和缝合线的 3D 代表性模型。我们展示了调节成骨细胞分化和骨形成过程中信号的单个参数的变化如何解释颅面畸形中颅顶形状的变异。一个关键的结果是，在我们的模型中切换一个参数会导致颅顶缝合线的闭合，这一事件发生在颅顶的进化过程中，也发生在颅面畸形中。我们的方法为将生物力学纳入基因型表型图谱提供了一个初始且重要的步骤，以解释发育机制对头骨形态变异的产生。
