Mechanical function of the primate craniofacial skeleton

该项目旨在建立计算机模型，使我们能够模拟和实验灵长类动物面部骨骼的生长，选择这些模型是因为它们在解剖学上与人类面部生长相似，因此提供了关于面部生长的信息。虽然遗传系统调节出生后颅面发育的早期，但后期发育受到机械负荷的强烈调控。颅面部骨骼对其直接的机械环境的反应是在骨骼(缝合线)处被动生长，以响应软组织(如大脑、舌头、肌肉)的扩张。它还通过建模和重塑机制来重新塑造，这些机制在机械环境的调节下，从表面添加和移除骨骼。重要的是，我们要理解这些机械调控的过程，因为它们不仅在正常增长中必不可少，在出现问题时也是必不可少的。此外，我们需要知道颅面形态的特征是如何在相关物种之间表现和变化的。我们的牙齿通常不适合我们的嘴巴，但在历史上却不是这样；发生了什么？答案可能在于改变更柔和的饮食，改变不断增长的脸部和随后的生长的机械负荷。更罕见的是，缝合线可能过早融合，或者颅骨软骨可能因为遗传性疾病而不能充分生长。随后头骨的生长必须适应改变的起始条件并优化功能。机械信号是其中的关键。了解机械调节应该能更好地预测正常和变化的生长，并理解面部骨骼的哪些特征是遗传的，哪些是适应局部力学的。这对于解决关于化石和现存物种之间关系的争论很重要。了解面部生长的机械规律的一种方法是进行实验，在实验中，动物接受手术，以切割肌肉、移动牙齿、切除结构等，并观察结果。这是一个非常有利可图的研究领域，特别是在我们最近的亲戚灵长类动物身上，但现在在英国进行这项工作在伦理和经济上都很困难。我们目前在这些领域的最佳信息来源来自欧洲以外的持续动物研究，特别是在美国。动物实验非常有用，但它们很难正确控制，而且进行和解释起来既费时又费时。如果我们有一个很好的面部和最终头骨生长的计算机模型，它们就可以被取代。虽然这样一个完整的模型还有很长的路要走，但我们计划在这个项目中模拟面部骨骼适应的机械调节，这将允许预测负荷改变的后果。这项工作将建立在我们在过去三年中开发的计算机模型的基础上，使用工程技术来预测载荷如何分布(有限元分析/有限元分析)。我们将把它们应用于两个相关的东半球猴子群体，猕猴和芒果猴，它们出生时脸部相似，但成年后发育出非常不同的特征。因此，猕猴在上颌骨发育出气窦，而芒果猕猴不会，相反，它们会在面部的外部--上颌窝--形成深层次的挖掘。我们将通过模拟我们已知的骨骼如何适应来扩展我们的模型，以便使用初始载荷来驱动模拟的骨沉积或吸收。然后，我们将用我们的计算机模型进行一系列实验，以测试关于面部形状特征发展的想法，并在这样做的过程中改进我们的模型和我们的理解。通过这种方式，我们将推进面部如何生长的知识，并开发将支持未来更完整的头面部发育模型的技术，这些模型最终将支持生长预测，适用于生物学、医学以及对人类和灵长类起源的研究。

This project aims to build computer models that allow us to emulate and experiment with growth of the facial skeleton in primates, chosen because they are anatomically similar to and therefore informative regarding human facial growth. Although genetic systems regulate the early part of post natal craniofacial growth, later development is strongly regulated by mechanical loading. The craniofacial skeleton responds to its immediate mechanical environment by passively growing where bones meet (the sutures) in response to the expansion of the soft tissues (e.g. brain, tongue, muscles). It is also resculpted by modelling and remodelling mechanisms that add and remove bone from surfaces, being modulated by the mechanical milieu. It is important we understand these mechanically regulated processes because they are essential not only in normal growth but also when things go wrong. Further we need to know how the features of craniofacial form that characterise and vary between related species come about. Commonly our teeth do not fit well to our mouths, yet in the historical past this was not the case; what has happened? The answer likely lies in the change to softer diets that alter the mechanical loading of the growing face and subsequent growth. More rarely sutures may fuse too early or skull cartilages may not grow adequately because of inherited conditions. The subsequent growth of the skull has to adapt to the altered starting conditions and optimise function. The mechanical signals are key in this. Understanding mechanical regulation should lead to better prediction of normal and altered growth and understanding of which features of the facial skeleton are inherited and which adapted to local mechanics. This is important in resolving arguments about the relationships among fossil and living species. One approach to understanding the mechanical regulation of the growth of the face is to carry out experiments in which animals are operated on to cut muscles, move teeth, excise structures etc and observe the outcomes. This has been a very profitable line of research especially in primates, our nearest relatives but now it is ethically and economically difficult to carry on this work in the UK. Our current best sources of information in these areas come from continuing animal studies outside Europe, especially in the USA. Animal experiments are very useful but they are difficult to properly control and lengthy and time consuming to carry out and interpret. They could be replaced if we had a good computer model of facial, and eventually, skull growth. While such a full model is long way off we plan in this project to emulate the mechanical regulation of facial bone adaptation that will allow prediction of the consequences of altered loading. The work will build on computer models that we have developed over the past three years employing engineering techniques for predicting how loads are distributed (finite elements analysis / FEA). We will apply them to two related old world monkey groups, macaques and mangabeys, with similar faces at birth that develop very different features of adult form. Thus macaques develop air sinuses in the maxilla but mangabeys do not, instead they develop deep excavations of the external aspect of the face, the maxillary fossae. We will extend our models by simulating what we know of how bone adapts so that initial loading is used to drive simulated bone deposition or resorption. We will then carry out a series of experiments with our computer models to test ideas about the development of features of facial form and in so doing work to improve our models and our understanding. In this way we will advance knowledge of how the face grows and develop technologies that will underpin future, more complete models of craniofacial development that will eventually underpin predictions of growth with applicability in biology, medicine and studies of human and primate origins.