Collaborative Research: Cranial Base Development in Primates

该项目将解决有关灵长类动物和人类生物学的问题，使用尖端可视化技术绘制出涉及各种灵长类动物颅骨软骨和骨骼生长和发育的细胞过程图。这个项目的发现将促进人们对颅骨生长决定整体头骨形状的方式的了解，这对于理解灵长类动物的适应和随时间推移的生活史非常重要。该项目将支持研究基础设施和年轻科学家的培训，并可能为患有颅脑畸形的儿童的临床研究和治疗提供信息。这项研究将颅底结构(包括颅底基本屈曲程度和面部朝向)的差异与生长过程的直接证据联系起来。九种灵长类动物被研究使用微型计算机断层扫描和组织学程序的新组合，以创建发育中的头骨的3D虚拟重建。颅底合并症的生长模式是通过测量软骨带的线性和横截面面积来量化的。围产期和大龄亚成人的颅骨形状使用体积、角度和基于地标的形态测量数据来描述。应用描述性统计和推论统计相结合的方法来解决四个具体目标：1)在灵长类动物的比较样本中描述围产期颅底的结构；2)记录促进生长的细胞和组织水平的机制的证据；3)测试围产期和成人颅底结构的系统发育效应；以及4)测试围产期和成人颅底生长模式与颅底角度和面部朝向的关系。这个项目是第一个通过直接观察软骨细胞增殖和肥大的指标来评估广泛灵长类动物出生后早期软骨开放或融合，并通过直接观察软骨细胞增殖和肥大的指标来促进对骨骼和软骨生长特征的了解。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.