Doctoral Dissertation Improvement: The Influence of Angiogenesis on Primate Cranial Vault Development and Evolution

这项跨学科的研究为灵长类动物和人类进化中已知的颅形态差异的发育基础提供了见解。该项目的独特之处在于，它检查了相关的发育系统（血管生成），以揭示颅骨进化变化的基础，而大多数其他研究都集中在更多的临床相关问题上。该项目训练本科生实验室技术，其结果对临床医学具有潜在价值。头骨反映了人类和非人类灵长类动物的一些最重要的进化趋势，提供了行为的证据，并反映了物种之间的进化关系。虽然对化石和现存灵长类动物的形态学研究为颅面形态的进化史提供了有价值的信息，但对产生形态学变异的特定发育机制的研究对于了解已知的进化变化是如何发生的是必要的。有强有力的证据表明，血管生长和发育（血管生成）在形成颅骨顶部的颅顶骨的发育中起着不可或缺的作用，其发育过程与人体大多数骨骼（膜内骨化）不同。本研究探讨了实验室小鼠在产前发育过程中血管生成和膜内骨化的相互作用，这是一个与灵长类动物共享发育过程的物种。了解这种相互作用提供了血管生成过程的变化如何影响颅面形态的信息，从而为理解人类和非人类灵长类动物颅骨的进化提供了信息。在发育期间，血管生成对形成性颅穹窿骨的影响可能是最强的，将携带已知导致人类穹窿骨畸形疾病的特定突变的小鼠的额骨与未受影响的窝鼠的额骨进行比较。血管发育的三维光声图像与骨的高分辨率计算机断层图像相结合，检测拱顶骨生长是否与血管生成有关并受血管生成的限制。

This interdisciplinary study provides insight into the developmental basis for known differences in cranial morphology noted across primate and human evolution. The project is unique in that it examines relevant developmental systems (angiogenesis) to uncover the basis of evolutionary change in the skull, while most other research into these processes focuses on more clinically relevant issues. The project is training undergraduates in laboratory techniques, and the results are potentially valuable to clinical medicine. The skull reflects some of the most important evolutionary trends of human and non-human primates, provides evidence of behavior, and reflects evolutionary relationships between species. While morphological studies of fossil and living primates have provided valuable information on the evolutionary history of craniofacial form, studies about the specific developmental mechanisms producing morphological variation are necessary to understand how known evolutionary changes occur. There is strong evidence that blood vessel growth and development (angiogenesis) plays an integral role in the development of the cranial vault bones that form the top of the skull and develop through a different process than most bones of the body (intramembranous ossification). This study investigates the interaction of angiogenesis and intramembranous ossification during prenatal development in laboratory mice, a species that shares developmental processes with primates. Understanding this interaction provides information of how changes in angiogenic processes influence craniofacial morphology, thereby informing understanding of evolution of the skull in human and non-human primates. The frontal bone of a mouse carrying specific mutations known to cause a human disease with vault bone dysmorphology is compared to that of unaffected littermates during the period of development when the influence of angiogenesis on formative cranial vault bone is likely to be the strongest. 3D photoacoustic images of developing blood vessels are combined with high resolution computed tomography images of bone testing whether vault bone growth is associated with and constrained by angiogenesis.