Doctoral Dissertation Research: Eluicidation of Growth Plate Dynamics via Immunohistochemistry of the Mammalian Metacarpal

灵长类动物的运动模式、栖息地和摄食策略主要取决于骨骼比例。要更全面地了解它们的进化，需要更好地了解控制它们发育的机制，并进一步了解它们的潜在细胞生长。为此，研究人员计划帮助阐明影响生长板结构及其在个体发育过程中行为的分子信号通路。在胚胎发生过程中调节软骨生长和成熟的机制（从而指导骨骼系统的形成）最近已经得到了很大的澄清。然而，这些相同的机制在正常的出生后生长中的作用在很大程度上仍然未知。一些骨骼通过直接添加材料生长，而另一些骨骼则有专门的纵向生长区域，称为生长板。哺乳动物的掌骨只形成一个生长板，因此另一端的行为就像没有生长板的骨头一样。因此，它提供了一个很好的模型来探索通过这两种不同的机制参与软骨生长和骨形成调节的分子信号如何不同，特别是环境潜力如何影响每一个。在小鼠出生后的多个年龄阶段掌骨的近端和远端之间的蛋白质表达（免疫组织化学）的比较可以照亮这些信号，并提供了一个更好的理解哺乳动物的生长规范的分子机制。 对生长板的出生后行为的更透彻的理解将直接提高我们对人类和灵长类动物骨骼进化（以及颅底的类似过程）的理解，以及骨骼长度（和形状）的变化如何在遗传上表达。因此，这项研究的目的是揭示基因的目标，自然选择修改的骨骼比例。这个研究项目有一个更广泛的影响，一般的科学，因为它需要人类学和生物医学研究人员之间的合作和互动，越来越多的必要性，因为生物子领域变得更加多样化和专业化。与往常一样，对正常生物学的了解的提高大大提高了我们加强临床护理的能力;鉴于人类生长障碍的多样性，目前的情况当然也不例外。 此外，该奖项将促进有前途的研究生的教育。

Skeletal proportions are primary to locomotor pattern, habitat, and feeding strategy in primates. A more complete understanding of their evolution requires better knowledge of the mechanisms that govern their development, and by extension, better comprehension of their underlying cellular growth. To this end, the researchers plan to help elucidate the molecular signaling pathways affecting structures known as growth plates and their behavior during ontogeny. The mechanisms that regulate cartilage growth and maturation during embryogenesis (and thus guide formation of the skeletal system) have recently been greatly clarified. However, the role of these same mechanisms in normal postnatal growth is still largely unknown. Some bones grow by direct addition of material while others have specialized areas for longitudinal growth called growth plates. The mammalian metacarpal forms only a single growth plate, such that the other end behaves like bones which lack them. Therefore, it provides an excellent model with which to explore how the molecular signals involved in the regulation of cartilage growth and bone formation via these two separate mechanisms differ, and especially how the environment potential affects each. Comparison of protein expression (immunohistochemistry) between the proximal and distal ends of metacarpals at multiple postnatal age stages in the mouse can illuminate these signals and provide a better understanding of the molecular mechanisms underlying growth specification in mammals. A more thorough understanding of postnatal behavior of growth plates will directly improve our understanding of both human and primate skeletal evolution (as well as similar processes in the base of the skull), and how changes in bone length (and shape) are genetically expressed. Thus, this study will aim to uncover genetic targets available to natural selection for the modification of skeletal proportions.This research project has a broader impact on science in general because it requires collaboration and interaction between anthropological and biomedical researchers, an increasing necessity as the biological subfields become more diverse and specialized. As always, an improved knowledge of normal biology greatly improves our ability to enhance clinical care; given the variety of growth disorders in humans, the present case is certainly no exception to this general rule. In addition this award will facilitate the education of a promising graduate student.