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

博士论文研究：进化和发育对骨骼成熟和内部结构的影响

基本信息

批准号：
1540418
负责人：
Philip Reno
金额：
$ 3.01万
依托单位：
Pennsylvania State Univ University Park
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2015
资助国家：
美国
起止时间：
2015-10-15 至 2017-09-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1540418&HistoricalAwards=false
关键词：
Doctoral Dissertation Research Evolutionary developmental

项目摘要

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.

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，也反映了由生活史造成的环境影响。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可以帮助推断现存和灭绝物种之间的行为和相关性。例如，在人类中，增大的跟骨或足跟骨及其扩张的骨小梁（海绵状）骨体积是与直立行走相关的众所周知的适应。相比之下，与其他灵长类动物相比，人类手腕中豌豆骨的急剧减少并没有得到很好的理解。这些是手腕和脚踝中唯一形成生长板的骨骼，这一事实表明，尽管它们在人类中的功能需求不同，但它们处于类似的发育控制之下。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，也将是整个宾夕法尼亚州中部的几个K-12学生和教育工作者外展计划的基础。跟骨的功能形态学研究，特别是它的骨小梁结构，是丰富的考虑到其关键作用的独特形式的运动中观察到的类人猿，但很少有人知道如何发展影响骨小梁结构。这项研究将探讨当发育基因突变改变生长时，骨小梁结构如何变化。将使用一项跨灵长类动物和小鼠外群的豌豆骨和跟骨骨化的比较研究来评估前肢和后肢之间的发育整合程度。将使用正常生长板小鼠和已知生长板异常的Hox 11功能丧失小鼠的跟骨CT扫描研究生长板结构对骨小梁的发育影响。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Influence of Hoxa11 and Hoxd11 on Calcaneus Growth and Ossification

Hoxa11和Hoxd11对跟骨生长和骨化的影响

DOI：
发表时间：
2021
期刊：
The FASEB journal
影响因子：
0
作者：
Bhavsar, Avani;Goldman, Samuel;Kjosness, Kelsey M;Schuetz, Emily;Kistler, Sabrina;Thompson, Ryan;Reno, Philip L
通讯作者：
Reno, Philip L

Identifying the homology of the short human pisiform and its lost ossification center

DOI：
10.1186/s13227-019-0145-2
发表时间：
2019-11-25
期刊：
EVODEVO
影响因子：
4.1
作者：
Kjosness, Kelsey M.;Reno, Philip L.
通讯作者：
Reno, Philip L.

Differential Impact of Hoxa11 and Hoxd11 on Pisiform Ossification and Epiphysis Formation

Hoxa11 和 Hoxd11 对豌豆骨骨化和骨骺形成的不同影响

DOI：
发表时间：
2021
期刊：
The FASEB journal
影响因子：
0
作者：
Graziano, Timothy;Sweeney, Brendan;Kjosness, Kelsey M;Kistler, Sabrina;Schuetz, Emily;Thompson, Ryan;Reno, Philip
通讯作者：
Reno, Philip

Morphological Changes in Calcanei of Mice with Hoxa11 and Hoxd11 loss-of-function mutations

Hoxa11 和 Hoxd11 功能丧失突变小鼠跟骨的形态变化

DOI：
发表时间：
2021
期刊：
The FASEB journal
影响因子：
0
作者：
Goldman, Samuel;Bhavsar, Avani;Kjosness, Kelsey M;Kistler, Sabrina;Schuetz, Emily;Stephens, Nicholas;Ryan, Timothy M;Reno, Philip L
通讯作者：
Reno, Philip L