Collaborative Research: Cranial Base Development in Primates

该项目将解决灵长类动物和人类生物学的问题，使用尖端的可视化技术来绘制涉及大范围灵长类动物颅骨软骨和骨骼生长和发育的细胞过程。这个项目的发现将推进关于颅骨生长决定整体头骨形状的方式的知识，这对于理解灵长类动物的适应和生活史很重要。该项目将支持研究基础设施和年轻科学家的培训，并可能为患有颅骨畸形的儿童的临床研究和治疗提供信息。本研究将颅底结构的差异（包括颅底屈曲程度和面部取向）与生长过程的直接证据联系起来。九种灵长类动物使用微型计算机断层扫描和组织学程序的新组合来创建发育中的头骨的3D虚拟重建进行研究。使用软骨带的线性和横截面积测量来量化颅底联合软骨的生长模式。围产儿和老年亚成人颅骨形状描述使用体积，角度和基于地标的形态测量数据。描述性统计和推理统计的结合应用于解决四个具体目标：1)描述灵长类动物比较样本的围产期颅底结构；2)记录细胞和组织水平机制促进生长的证据；3)围产期颅底结构的系统发育效应检验；4)检测围生期和成人颅底生长模式与颅底角和面相的关系。该项目首次在广泛的灵长类动物中评估出生后早期软骨联合开放或融合，并通过直接观察软骨细胞增殖和肥大这两个驱动间质生长的指标，促进对骨和软骨生长特征的理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project will address questions about primate and human biology using cutting-edge visualization techniques to map the cellular processes involved in growth and development of cranial cartilage and bone across a wide range of primates. Findings from this project will advance knowledge about the ways in which cranial growth determines overall skull shape, which is important for understanding primate adaptations and life history through time. The project will support research infrastructure and training of young scientists, and may inform clinical research and treatments for children with cranial malformations.This study relates differences in cranial base structure (including degree of basicranial flexion and facial orientation) to direct evidence of growth processes. Nine primate species are studied using a novel combination of micro-computed tomography and histological procedures to create 3D virtual reconstructions of the developing skull. Growth patterns in cranial base synchondroses are quantified using linear and cross-sectional area measurements of cartilaginous zones. Cranial shape in perinatal and older subadults is described using volumetric, angular, and landmark-based morphometric data. A combination of descriptive and inferential statistics are applied to address four specific aims: 1) describe the structure of the perinatal cranial base in a comparative sample of primates; 2) document evidence of cellular and tissue-level mechanisms contributing to growth; 3) test for a phylogenetic effect in perinatal cranial base structure; and 4) test the association of cranial base growth patterns with cranial base angle and facial orientation in the perinatal period and in the adult. This project is the first to assess early postnatal synchondroseal patency or fusion in a broad range of primates and advance understanding of growth characteristics of bone and cartilage by directly observing indicators of chondrocyte proliferation and hypertrophy, two drivers of interstitial growth.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.