Investigating Organ Formation and the Emergence of Complexity in the Visual System Using Comparative Developmental Approaches

使用比较发育方法研究器官形成和视觉系统复杂性的出现

• 批准号: 9355706
• 负责人: Kristen Marie Koenig
• 金额: $ 42.25万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355706
• 关键词: Ablation; Address; Animal Model; Animals; Architecture; Bioinformatics; Candidate Disease Gene; Cell Differentiation process; Cells; Cellular biology; Cnidaria; Complex; Data Set; Development; Developmental Biology; Disease; Drosophila genus; Embryo; Evolution; Eye; Eye Development; Family member; Generations; Genes; Genetic; Goals; Health; Heart Research; Human; Image; Light; Modeling; Molecular; Morphogenesis; Morphology; Movement; Nervous system structure; Neuroepithelial Tissue; Organ; Pathway Analysis; Pathway interactions; Pharmacotherapy; Phylogenetic Analysis; Play; Process; Protocols documentation; Recording of previous events; Regulator Genes; Research; Retina; Retinal; Role; Signal Transduction; Structure; Surface; System; Time; Tissues; Transfection; Translating; Vertebrates; Vesicle; Visual; Visual system structure; Work; body system; cell behavior; cell type; comparative; comparative genomics; darwinism; experimental study; eye formation; in vivo; in vivo imaging system; member; notch protein; organ growth; protein function; relating to nervous system; response; tool; transcriptome sequencing; vision development

Project Summary: Investigating Organ Formation and the Emergence of Complexity in the Visual System Using Comparative Developmental Approaches The visual system has long been at the heart of research into the evolution of complexity in the animal kingdom. Even Darwin in On the Origin of Species addressed the evolution of the vertebrate eye as a unique and difficult case in the study of evolution. Despite a long history of research in Drosophila and vertebrate models, we still understand surprisingly little about how complex organ systems like the visual system are generated. For example, we have long known that Pax6 and other retinal determination network genes are essential to eye development in both Drosophila and vertebrates, suggesting a common origin for all visual organs. However, differences in gene regulatory network connectivity support independent evolution of parts of this canonical network. This highlights our lack of understanding of how networks change and how they relate to the complex tissues they underlie. Here we propose to leverage comparative developmental biology to better understand how gene regulatory networks, protein function, cell fate, and tissue movements evolved to generate the complexity and diversity within photoreceptive systems found across the animal kingdom. The power of comparative approaches is that they can reveal non-obvious and conserved mechanisms found common to organ formation. Recognizing these mechanisms not only deepens our basic understanding of complex organ development, it can generate new disease candidates and practical new models for human health. First, we will investigate how complex morphologies of visual organs develop by evaluating cell behavior and tissue morphogenesis during eye vesicle formation in the cephalopod Doryteuthis pealeii. Second, we will identify conserved mechanisms generating cell type diversity within the retina, specifically focused on Notch signaling in neuroepithelial tissues. Lastly, we will evaluate the core retinal determination gene regulatory network across the animal kingdom using both functional and bioinformatics tools to identify conserved network connections. This work will be the most in depth analysis to date of the relationship between gene regulatory networks to cell differentiation and tissue morphogenesis across multiple species. Our current lack of understanding of this relationship generates a barrier to translate research in model organisms to effective disease treatment efficiently and this work will shed light on better approaches to these translational steps.

项目概要：研究器官形成和视觉中复杂性的出现 采用比较发展方法的系统 长期以来，视觉系统一直是研究动物复杂性进化的核心 王国即使是达尔文在《物种起源》中也把脊椎动物眼睛的进化作为一种独特的 也是进化论研究中的一个难题尽管对果蝇和脊椎动物的研究历史悠久 尽管我们对视觉系统等器官系统的复杂程度了解甚少， 生成的.例如，我们早就知道Pax6和其他视网膜决定网络基因是 在果蝇和脊椎动物的眼睛发育中至关重要，这表明所有视觉器官都有一个共同的起源。 机关然而，基因调控网络连通性的差异支持了部分基因的独立进化。 这个典型的网络。这凸显了我们对网络如何变化以及它们之间如何联系的理解不足 到它们背后的复杂组织。在这里，我们建议利用比较发育生物学， 更好地了解基因调控网络，蛋白质功能，细胞命运和组织运动是如何进化的， 在整个动物王国的感光系统中产生复杂性和多样性。的 比较方法的力量在于，它们可以揭示发现的不明显和保守的机制， 器官形成的共同点。认识到这些机制不仅加深了我们对 复杂的器官发育，它可以产生新的疾病候选人和实用的新模型，为人类 健康首先，我们将通过评估细胞来研究视觉器官的复杂形态是如何发展的。 头足类Doryteuthis pealeii眼泡形成过程中的行为和组织形态发生。 其次，我们将确定保守的机制，产生细胞类型的多样性视网膜内，具体来说， 专注于神经上皮组织中的Notch信号传导。最后，我们将评估核心视网膜的决定， 跨动物王国的基因调控网络，使用功能和生物信息学工具来识别 保持网络连接。这项工作将是迄今为止对这种关系最深入的分析 基因调控网络与多个物种的细胞分化和组织形态发生之间的联系。 我们目前缺乏对这种关系的理解，这对将研究转化为模型产生了障碍 生物有效的疾病治疗有效，这项工作将揭示更好的方法，这些 平移步骤