ABSTRACT

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.

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