CAREER: The Developmental Regulation of Amniote Skull Diversity

职业：羊膜动物头骨多样性的发育调控

• 批准号: 1942250
• 负责人: Thomas Sanger
• 金额: $ 96.46万
• 依托单位: Loyola University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942250&HistoricalAwards=false
• 关键词: CAREER; Developmental; Regulation; Amniote; Skull

As vertebrates moved into new ecological spaces the skull diversified in size, shape, and became adorned with ornaments and weapons. It is no surprise, therefore, that the skull has fascinated researchers across the entirety of Biology over the past century. In more recent decades, understanding the developmental bases of craniofacial diversity has been a major goal of Evolutionary-developmental biology. However, a paucity of experimental systems among amniotes – reptiles, birds, and mammals – has made it difficult to create a synthetic understanding of how developmental patterning has changed during the remarkable diversification in skull form. In this research Dr. Sanger will dissect skull development in an emerging model lizard, Anolis sagrei. Sanger and his team will investigate the expression and function of three core signaling pathways known to be involved in skull development in other amniote species. Through this research they will discover whether the diversity in skull form is due to minor or major changes in craniofacial patterning. Capitalizing on the inherent interest in the vertebrate skull, Sanger will also team with a group of professional educators to develop "Getting Ahead in Life: Investigations into the Vertebrate Skull", cutting-edge, transdisciplinary learning modules targeted to upper level high school and undergraduate biology. Embedded within these modules will be interviews and real-world data from leaders in the field of craniofacial biology, especially people from groups underrepresented in STEM. Together, Sanger’s efforts will significantly advance the field of craniofacial development and help motivate the next generation of students to pursue education in STEM fields.One of the most morphologically and developmentally complex anatomical systems is the vertebrate skull. Although there is coarse similarity in cranial embryology among these groups, there is growing, yet disparate, evidence to suggest that cranial patterning has evolved over both small and large evolutionary scales. To date, however, our understanding of facial development has primarily arisen from only a few experimentally accessible avian and mammalian species, making it difficult to make broad generalizations about the evolution of cranial development. Uncovering the function of key patterning genes in previously undescribed clades is a critical step towards polarizing the evolution of cranial patterning mechanisms and to help elucidate the ancestral character state of amniotes. In this research Sanger and his team will investigate the expression and function of three core signalizing pathways involved in craniofacial development: Hedgehog, Fibroblast growth Factor, and Bone morphogenetic protein. This team will use new tools to manipulate the expression of these pathways in embryos of Anolis sagrei, an emerging model system in Developmental Biology, but a historically important species in Ecology and Evolutionary Biology. With this baseline information in hand, Sanger will turn towards evolutionary patterns of skull diversity on a smaller scale, among Anolis lizards. Anolis lizards vary extensively in their facial length. Multiple lineages have independently converged on short-faced and long-faced morphologies. Sanger and his team will also determine the developmental bases of these convergent phenotypes. Combined, this research will determine how the processes regulating craniofacial development evolve over different evolutionary time scales.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.

随着脊椎动物进入新的生态空间，头骨在大小、形状上多样化，并开始装饰着装饰品和武器。因此，在过去的一个世纪里，这个头骨吸引了整个生物学领域的研究人员，这并不令人惊讶。近几十年来，了解颅面部多样性的发育基础一直是进化发育生物学的主要目标。然而，在羊膜动物--爬行动物、鸟类和哺乳动物--中缺乏实验系统，这使得我们很难对发育模式在头骨形态显著多样化期间发生了怎样的变化做出综合的理解。在这项研究中，桑格博士将解剖一种新兴的模式蜥蜴--Anolis sgrei--的头骨发育。桑格和他的团队将研究在其他羊膜动物物种中参与头骨发育的三个核心信号通路的表达和功能。通过这项研究，他们将发现头骨形状的多样性是由于颅面图案的微小变化还是重大变化。利用人们对脊椎动物头骨的固有兴趣，桑格还将与一群专业教育工作者合作，开发针对高中和本科生物学的尖端、跨学科的学习模块《出人头地：脊椎动物头骨调查》。这些模块中将嵌入来自颅面生物学领域领导者的采访和真实世界数据，特别是来自STEM代表性不足的群体的人。总之，桑格的努力将极大地推动颅面发育领域的发展，并有助于激励下一代学生在STEM领域进行教育。脊椎动物头骨是形态和发育最复杂的解剖系统之一。尽管这些群体在颅骨胚胎学上有粗略的相似之处，但有越来越多但不同的证据表明，颅骨模式在小范围和大范围的进化中都已进化。然而，到目前为止，我们对面部发育的了解主要来自少数可通过实验获得的鸟类和哺乳动物物种，因此很难对颅骨发育的进化做出广泛的概括。揭示以前未被描述的分支中的关键模式基因的功能是分化颅骨模式机制进化的关键一步，并有助于阐明羊膜动物的祖先特征状态。在这项研究中，桑格和他的团队将研究与颅面发育有关的三个核心信号通路的表达和功能：刺猬、成纤维细胞生长因子和骨形态发生蛋白。这个团队将使用新的工具来操纵这些途径在Anolis sgrei胚胎中的表达，Anolis sgrei是发育生物学中的一个新兴模式系统，但在生态学和进化生物学中是一个历史上重要的物种。有了这一基线信息，桑格将转向Anolis蜥蜴中较小规模的头骨多样性的进化模式。Anolis蜥蜴的面部长度差异很大。多个谱系独立地汇聚在短面和长面形态上。桑格和他的团队还将确定这些趋同表型的发育基础。综合考虑，这项研究将确定调节颅面发育的过程如何在不同的进化时间尺度上演变。这一奖项反映了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。