Doctoral Dissertation Research: Evolutionary and developmental influences on skeletal maturation and internal structure

一个特定物种的骨骼形状既反映了由基因决定的发育遗传过程，也反映了由生命史产生的环境影响。在对灵长类动物和人类的研究中，了解这些过程的相对贡献有助于推断现存和灭绝物种之间的行为和关系。例如，在人类中，随着小梁（海绵状）骨体积的扩大，跟骨或脚跟骨的扩大是一种众所周知的直立行走的适应。相比之下，与其他灵长类动物相比，人类手腕的梨状骨的急剧减少并没有得到很好的认识。事实上，腕部和踝关节中只有这些骨骼形成生长板，这表明尽管它们在人类身上的功能需求不同，但它们在相似的发育控制下。因此，这些骨骼形成了一个理想的模型，以确定遗传模式和生活史对骨骼形状的不同影响。增加对骨骼生长差异如何影响骨骼形状的了解也可能提高我们对骨骼疾病病因学的理解。这项工作将用于培训一名女研究生和几名本科生，也将成为宾夕法尼亚州中部几个K-12学生和教育工作者外展项目的基础。跟骨的功能形态学研究，特别是它的骨小梁结构，在类人猿中观察到的独特运动形式中起着关键作用，但关于发育如何影响骨小梁结构的研究很少。本研究将探讨发育基因突变改变生长时小梁结构的变化。在类人猿灵长类动物和小鼠外群中进行的一项梨状骨和跟骨骨化的比较研究将用于评估前肢和后肢之间发育整合的程度。生长板结构对小梁骨的发育影响将通过CT扫描正常生长板小鼠和已知生长板异常的Hox11功能缺失小鼠的跟骨来研究。

The shape of the skeleton for a given species reflects both developmental genetic processes dictated by genes and environmental influences resulting from life history. In studies of primates and humans, understanding the relative contributions of these processes can help in making inferences about behavior and relatedness among both living and extinct species. For example, in humans, the enlarged calcaneus, or heel bone, with its expanded trabecular (spongy) bone volume is a well-known adaptation associated with walking upright. In contrast, the dramatic reduction of the pisiform bone in the in human wrist compared to other primates is not well appreciated. The fact that these are the only bones of the wrist and ankle to form growth plates suggests that they are under similar developmental control despite their different functional demands in humans. As such these bones form an ideal model to determine differential effects of genetic patterning and life history on skeletal shape. Increased knowledge of how differences in skeletal growth affect bone shape may also improve our understanding of the etiology of skeletal disease. This work will be used to train a female graduate student and several undergraduates, and will also be the basis of several K-12 student and educator outreach programs throughout central Pennsylvania. Functional morphological studies of the calcaneus, and specifically its trabecular bone structure, are abundant given its critical role in the unique forms of locomotion observed in hominoids, but little is known about how development influences trabecular structure. This study will investigate how trabecular structure changes when growth is altered by mutations in developmental genes. A comparative study of pisiform and calcaneus ossification across anthropoid primates and a mouse outgroup will be used to assess degree of developmental integration between the fore and hind limbs. Developmental effects of growth plate structure on trabecular bone will be studied using CT scans of calcanei from mice with normal growth plates and Hox11 loss-of-function mice with known growth plate abnormalities.