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

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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.