Testing Models of Jaw Joint Evolution Using the Sea Lamprey, Xenopus laevis, and zebrafish

使用海七鳃鳗、非洲爪蟾和斑马鱼测试下颌关节进化模型

• 批准号: 1656843
• 负责人: Daniel Medeiros
• 金额: $ 60万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-15 至 2021-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656843&HistoricalAwards=false
• 关键词: Testing; Models; Jaw; Joint; Evolution

Jawed vertebrates evolved from jawless fish a half-billion years ago and have since become one of the most successful animal groups on the planet. This project aims to understand how jawed vertebrates evolved from jawless fish. This will be done by comparing the development of the modern jawless fish, lamprey, with that of two jawed vertebrates, the african clawed frog, and the zebrafish. To do this, modern methods for manipulating gene function will be used to alter the activity of genes involved in head skeleton development. These manipulations are aimed at partially recapitulating the evolutionary process and pinpointing which genes were most important for jaw evolution. The work will shed light on a major evolutionary event that made possible the evolution of the majority of vertebrates now living on the planet, including humans. The project will also help elucidate how the head skeleton and jaw develops in all vertebrates and contribute to efforts to understand the developmental and genetic basis of diseases effecting the face, skull, and jaw. Additionally, the project will provide training in modern genome engineering methods for a postdoctoral scholar, two graduate students, and several undergraduate and high school students. It will also support the maintenance of a traveling museum exhibit about animal development and evolution, and accompanying public lectures by the lead investigator.The morphology of early vertebrate fossils, and basally-diverging modern vertebrates, suggests that jaw evolution involved two major changes in head skeleton structure; the evolution of morphologically distinct dorsal and ventral skeletal elements, and the positioning of flexible joint tissue between these elements. How, mechanistically, these changes occurred, is unclear. In gnathostomes, head skeleton precursors are segregated early in development into dorsal, ventral, and intermediate domains by interactions between Jagged-Notch, BMP, and Endothelin (Edn) signaling pathways. These signals regulate the combinatorial expression of Dlx, Msx, and Hand transcription factors which, in turn, activate the morphogenetic and differentiation programs that shape skeletal elements and specify joints. To better understand the developmental changes underlying gnathostome head skeleton evolution, this research will utilize the living agnathan, lamprey. Lamprey is the only extant jawless vertebrate amenable to routine embryonic manipulations. Initial gene expression studies suggested that lamprey lacks dorso-ventral restricted expression of Dlx paralogs in head skeleton precursors. Subsequent work revealed unexpectedly gnathostome-like expression of Edn signaling components, Dlx, Msx, and Hand in the forming lamprey head. Furthermore, it was found that a lamprey homolog of the joint tissue specifier, Gdf5, is expressed in mucocartilage, a soft, mesenchymal skeletal tissue histologically similar to gnathostome joint tissue. These data supported a model in which; 1) a sophisticated gnathostome-type head skeleton patterning system predates the evolution of jaws and 2) the evolution of joints was driven by the repositioning of ancient gene programs for soft skeletal tissue differentiation within this conserved pre-pattern. The proposed work will take advantage of recent optimization of CRISPR/Cas9 mutagenesis in lamprey to test key predictions of this model in the sea lamprey Petromyzon marinus, and the frog Xenopus laevis.

有颌脊椎动物在5亿年前从无颌鱼进化而来，自那以来已经成为地球上最成功的动物群体之一。这个项目旨在了解有颌脊椎动物是如何从无颌鱼进化而来的。这将通过比较现代无颌鱼类七鳃鳗和两种有颌脊椎动物非洲爪蛙和斑马鱼的发育来完成。要做到这一点，现代控制基因功能的方法将被用来改变参与头骨发育的基因的活动。这些操作的目的是部分概括进化过程，并准确指出哪些基因对颌骨进化最重要。这项工作将揭示一项重大的进化事件，这一事件使目前生活在地球上的大多数脊椎动物，包括人类的进化成为可能。该项目还将有助于阐明所有脊椎动物的头部、骨骼和颌骨是如何发育的，并有助于了解影响面部、头骨和颌骨的疾病的发育和遗传基础。此外，该项目将为一名博士后学者、两名研究生以及几名本科生和高中生提供现代基因组工程方法方面的培训。它还将支持维持一个关于动物发展和进化的博物馆巡回展览，以及伴随首席研究员的公开讲座。早期脊椎动物化石和基本分化的现代脊椎动物的形态表明，颌骨进化涉及头骨结构的两个主要变化；形态上不同的背侧和腹侧骨骼元素的演变，以及这些元素之间柔性关节组织的位置。从机制上讲，这些变化是如何发生的，目前尚不清楚。在脊椎动物中，头部骨骼前体通过锯齿状Notch、BMP和内毒素(EDN)信号通路之间的相互作用，在发育早期被分离到背侧、腹侧和中间区域。这些信号调节DLX、MSX和手部转录因子的组合表达，而手部转录因子反过来激活形态发生和分化程序，形成骨骼元素和指定关节。为了更好地了解咬口鱼头部骨骼进化背后的发育变化，本研究将利用活的七鳃鳗。七鳃鳗是现存的唯一一种可以接受常规胚胎操作的无颌脊椎动物。最初的基因表达研究表明，七鳃鳗在头骨前体中缺乏DLX类似物的背腹限制性表达。随后的工作揭示了EDN信号组件DLX、MSX和Hand在形成的七鳃鳗头部意外地表达。此外，还发现关节组织指定子Gdf5的Lamprey同源基因在粘液中表达，粘液是一种柔软的间质骨骼组织，在组织学上类似于颌骨关节组织。这些数据支持这样一个模型：1)在颌骨进化之前，一个复杂的颌口型头部骨骼图案系统；2)关节的进化是由古老的软骨骼组织分化基因程序在这个保守的前图案中重新定位驱动的。这项拟议的工作将利用最近对七鳃鳗CRISPR/Cas9突变的优化来测试该模型在七鳃鳗Petromyzon marinus和非洲爪蛙中的关键预测。

项目成果

Evolution of the endothelin pathway drove neural crest cell diversification

• DOI: 10.1038/s41586-020-2720-z
• 发表时间: 2020-09-16
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Square, Tyler A.;Jandzik, David;Medeiros, Daniel M.
• 通讯作者: Medeiros, Daniel M.

Comparative Approaches in Vertebrate Cartilage Histogenesis and Regulation: Insights from Lampreys and Hagfishes

• DOI: 10.3390/d13090435
• 发表时间: 2021-09
• 期刊: Diversity
• 作者: Zachary D. Root;C. Gould;Margaux Brewer;D. Jandzik;Daniel M. Medeiros

Evolution of vertebrate gill covers via shifts in an ancient Pou3f3 enhancer

• DOI: 10.1073/pnas.2011531117
• 发表时间: 2020-10-06
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Barske, Lindsey;Fabian, Peter;Crump, J. Gage
• 通讯作者: Crump, J. Gage

Lamprey lecticans link new vertebrate genes to the origin and elaboration of vertebrate tissues

• DOI: 10.1016/j.ydbio.2021.03.020
• 发表时间: 2021-05-01
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Root，Zachary D.;Jandzik，David;Medeiros，Daniel M.
• 通讯作者: Medeiros，Daniel M.