Doctoral Dissertation Research: Dissecting the effect of encephalization on skull morphogenesis

古人类的颅容量有了显著的增长。这些相对脑大小的变化被假设为导致（1）现代人类头骨的改变和（2）可能影响头骨发育的躯体生长延迟或减少。虽然先前的研究使用化石或比较灵长类动物数据来了解大脑和头骨之间的关系，但该项目利用实验方法将脑化过程与头骨形态的特定变化联系起来。该项目的成果将被纳入多种教育和推广活动，旨在激发年轻学生，特别是年轻女性对STEM领域和职业的兴趣，并促进对生物人类学跨学科潜力的认识。通过宾州州立大学为女性举办的扩大你的视野STEM职业日和ScienceU Pre-Med Expo，研究人员将帮助学生了解随着时间的推移，人类头骨中发生的形态变化，包括脑化的具体影响。该项目使用BAF 170小鼠模型，该模型具有已知的导致大脑扩大表型的遗传变异。BAF 170基因仅在皮质组织中被敲除，导致皮质增大，使得头骨中的任何变化只能归因于较大皮质的影响。利用产前和出生后早期颅骨发育的高分辨率显微计算机断层扫描数据，这项研究将测试相对大脑大小的增加是否会影响颅骨的躯体生长或导致颅骨发育或最终形态的变化。实验旨在确定大脑大小的变化是否会导致以下方面的变化：（1）胚胎发育期间颅骨骨化中心出现/形成的时间;（2）颅骨质量，通过定量骨体积和骨密度进行评估;或（3）颅底，颅穹窿或面部骨骼的形态，可以与人类在时间上观察到的类似变化进行比较。这些实验将通过检查大脑大小与颅底角之间的关系以及大脑大小变化与躯体个体发育轨迹之间的关系来检验空间填充假说和昂贵大脑假说。由此产生的数据将提供实验证据，有关脑化在古人类和头骨形态和生长产生的独特的人类头骨表型的变化之间的关系。

Dramatic increases in cranial capacity have occurred in hominins. These shifts in relative brain size are hypothesized to have caused (1) alterations to the modern human skull and (2) delays or reductions in somatic growth that may affect skull development. While prior studies have used fossil or comparative primate data to understand the relationship between the brain and skull, this project utilizes an experimental approach to link the process of encephalization with specific changes in skull morphology. The results of this project will be incorporated into multiple educational and outreach activities designed to stimulate interest in younger students pursuing STEM fields and careers, particularly young women, and foster awareness of the interdisciplinary potential for biological anthropology. Through the Penn State Expanding Your Horizons STEM Career Day for Women and the ScienceU Pre-Med Expo, the researchers will help students understand the morphological changes that have occurred in the human skull over time, including the specific impact of encephalization.This project uses the BAF170 murine model with a known genetic variant that results in an enlarged brain phenotype. The BAF170 gene is knocked-out only in cortical tissue resulting in an enlarged cortex, such that any changes in the skull can only be attributed to the effect of the larger cortex. Using high-resolution micro-computed tomography data of prenatal and early postnatal skull development, this research will test whether an increase in relative brain size affects somatic growth of the skull or causes changes in cranial development or eventual morphology. Experiments are designed to determine whether the change in brain size causes changes in: (1) the timing of the appearance/formation of cranial ossification centers during embryological development; (2) cranial bone quality, evaluated by quantifying bone volume and bone density; or (3) morphology of the cranial base, cranial vault, or facial skeleton that can be compared with similar changes seen through time in hominins. These experiments will test the spatial packing hypothesis and the expensive brain hypothesis, by examining the relationship between brain size and cranial base angle and between changes in brain size and somatic ontogenetic trajectories. The resulting data will provide experimental evidence pertaining to the relationship between encephalization in hominins and changes in skull morphology and growth producing the unique human skull phenotype.