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

古人类的脑容量急剧增加。这些相对大脑大小的变化被假设造成了(1)现代人颅骨的改变和(2)可能影响颅骨发育的躯体生长的延迟或减少。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，特别是年轻女性对从事STEM领域和职业的兴趣，并培养对生物人类学跨学科潜力的认识。通过宾夕法尼亚州立大学拓展女性STEM职业日和科学预科医学博览会，研究人员将帮助学生了解人类头骨随着时间的推移发生的形态学变化，包括脑化的具体影响。该项目使用具有已知遗传变异的BAF170小鼠模型，导致大脑表型增大。BAF170基因只在皮质组织中被敲除，导致皮质变大，因此头骨的任何变化都只能归因于皮质变大的影响。利用产前和产后早期颅骨发育的高分辨率微型计算机断层扫描数据，本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。实验旨在确定脑大小的变化是否会导致以下方面的变化：(1)胚胎发育过程中颅骨骨化中心出现/形成的时间；(2)颅骨骨质量，通过量化骨量和骨密度评估；或(3)颅底、颅顶或面部骨骼的形态，可以与古人类的类似变化进行比较。这些实验将通过研究脑大小与颅底角之间的关系，以及脑大小变化与躯体个体发生轨迹之间的关系，来检验空间填充假说和昂贵脑假说。由此产生的数据将为人类脑化与颅骨形态和生长变化之间的关系提供实验证据，从而产生独特的人类颅骨表型。

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.