CAREER: Evo-Developmental Interactions of Craniofacial and Brain Anatomy

大约每1,500个新生儿中就有一个被诊断为先天性脑积水，过量的脑脊液导致大脑膨胀，然后导致周围的头骨肿胀。这种脑-颅相互作用证实了组织类型之间相互作用的普遍性和复合效应。然而，大多数解剖学研究中使用的分析将每个组织视为独立的孤立实体。忽视组织与组织之间的相互作用会阻碍对导致沿着发育和进化时间线的解剖学变化的因素的真正诊断。为了使用现代技术解决这个问题，拟议的研究包括两个关于大脑-头骨相互作用的互补项目。第一项研究涉及收集和分析350种鸟类的高密度大脑和头骨形状数据，以了解大脑和头骨如何指导彼此的进化轨迹。为了查明大脑和头骨相互作用的机制，第二项研究包括对一种具有奇怪形状的大脑和头骨的新型鸟类模式生物进行胚胎学实验。总的来说，这些项目将展示组织与组织之间的相互作用对新的和不同的解剖形式的出现的贡献。除了其科学价值外，该研究还将通过开发和实施（i）基于项目的胚胎学模块到新生的研究生课程中培养科学，技术，工程，艺术和数学（STEAM）人才;（ii）新的虚拟现实（VR）和3D益智游戏;以及（iii）科学数据的音乐表达，以吸引更具包容性的观众，包括种族和少数民族，残疾人，达尔文主义范式支持适应性选择作为特征进化的关键过程的作用。然而，最近的大规模进化研究表明，功能和生态变量占结构的总形态多样性的非常适度的金额。如果生态和功能只占总表型差异的一小部分，那么在漫长的时间里，多样化的主要驱动力是什么？本研究不是分析单个结构，而是将结构之间的相互作用作为一个基本过程来解释性状的统一性和多样性。使用大脑和颅面解剖学作为一个示范系统，该项目包括（i）收集为基础的跨鸟类生命树的脑-颅骨整合种间分析;和（ii）对一对鸡品种的观察和操纵发育研究，一个异常的大脑和颅骨形态。通过经典和现代技术的综合，包括计算机断层扫描（CT）成像，高密度形状分析，体内胚胎学和荧光显微镜，这些研究将可视化，建模和测试大脑和头骨之间的进化和发育相互作用跨越多个尺度，从亚细胞到总体解剖水平。重要的是，这些技术和由此产生的科学数据将汇集在三个拟议的教育计划中：（i）一个新的以项目为重点的胚胎学模块，用于新生的研究生课程;（ii）一个沉浸式虚拟现实（VR）游戏和相关的3D打印拼图;以及（iii）将生物数据转换为音乐的STEAM项目，该奖项反映了NSF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。

Approximately one in 1,500 newborns are diagnosed with congenital hydrocephalus where excess cerebrospinal fluid leads to an expanded brain, which then causes the surrounding skull to swell. This brain-to-skull interaction exemplifies the prevalence and compounding effects of interactions between tissue types. Nevertheless, analyses used in most anatomical studies treat each tissue as independent, isolated entities. Disregarding tissue-to-tissue interactions impedes true diagnoses of factors that contribute to anatomical changes along developmental and evolutionary timelines. To address this issue using modern techniques, the proposed research features two complementary projects on brain-skull interactions. The first study involves collection and analysis of high-density brain and skull shape data across 350 bird species to understand how the brain and skull have directed each other’s evolutionary trajectories. To pinpoint the mechanisms governing brain and skull interactions, the second study comprises embryological experiments on a novel avian model organism with a bizarrely shaped brain and skull. Collectively, these projects will demonstrate the contribution of tissue-to-tissue interactions on emergence of novel and diverse anatomical forms. Beyond its scientific merit, the research will also foster Science, Technology, Engineering, Art, and Mathematics (STEAM) talent through development and implementation of (i) a project-based Embryology module into a nascent graduate program; (ii) new virtual reality (VR) and 3-D puzzle games; and (iii) musical expressions of scientific data to engage more inclusive audiences, including racial and ethnic minorities, people with disabilities, and artistically inclined non-expert audiences.The Darwinian paradigm champions the role of adaptive selection as a key process underlying trait evolution. However, recent large-scale evolutionary studies have shown that functional and ecological variables account for very modest amounts of the total morphological diversity of a structure. If ecology and function account for only a small proportion of the total phenotypic disparity, what are the major drivers of diversification through deep time? Instead of analyzing a single structure, this research focuses on the interactions between structures as a fundamental process that accounts for the unity and diversity of traits. Using the brain and craniofacial anatomy as an exemplar system, the project comprises (i) a collection-based interspecific analysis of brain-skull integration across the avian tree of life; and (ii) observational and manipulative developmental studies on a pair of chicken breeds, one with aberrant brain and skull morphologies. Through a synthesis of classic and modern techniques, including computed tomography (CT) imaging, high-density shape analysis, in vivo embryology, and fluorescence microscopy, these studies will visualize, model, and test evolutionary and developmental interactions between brains and skulls across multiple scales, from subcellular to gross anatomical levels. Importantly, these techniques and the resulting scientific data will converge on three proposed education initiatives: (i) a new project-focused Embryology module for a nascent graduate program; (ii) an immersive virtual reality (VR) game and an associated 3D-printed puzzle; and (iii) a STEAM project that translates biological data into music, offering a new modality to express and teach scientific concepts.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.