Determining the genetic and developmental basis of epidermal appendage evolution

确定表皮附属物进化的遗传和发育基础

• 批准号: 8524600
• 负责人: Eric Domyan
• 金额: $ 4.92万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8524600
• 关键词: Adult; Ankle; Area; Back; Biochemical; Biology; Birds; Body Size; Breeding; Candidate Disease Gene; Cell Maintenance; Cells; Characteristics; Color; Columbidae; Communication; Coupled; Data; Defect; Development; Disease; Embryo; Embryonic Development; Eph Family Receptors; Epithelial; Event; Evolution; Feathers; Gene Expression; Genes; Genetic; Genetic Crosses; Genetic Polymorphism; Genomics; Goals; Growth; Hair; Head; Homeostasis; Human; In Vitro; Individual; Lead; Location; Locomotion; Malignant Neoplasms; Mammals; Maps; Mesenchymal; Microsurgery; Modeling; Molecular; Morphology; Nature; Organ; Organism; Pattern Formation; Physiologic Thermoregulation; Population; Prevention; Price; Process; Public Health; Quantitative Trait Loci; Receptor Signaling; Research; Rock Pigeons; Role; Sebaceous Glands; Signal Transduction; Skin; Stem cells; Structure; Study models; Techniques; Testing; Tissue Grafts; Tissue Recombination; Tissues; Variant; Visual; Wing; Work; Wound Healing; appendage; base; craniofacial; developmental genetics; fitness; foot; gene function; genetic manipulation; insight; interest; molecular phenotype; novel; public health relevance; research study; stem cell biology; stem cell population; tissue regeneration; trait

DESCRIPTION (provided by applicant): The development of epidermal appendages, such as hair in mammals and feathers and scales in birds, provides a particularly tractable model for studying medically-relevant processes such as fate determination, epithelial-mesenchymal interactions, stem cell maintenance, and lineage commitment. In adult organisms, disregulation of appendage homeostasis can lead to diseases such as cancer, highlighting the importance of understanding how development is controlled. In addition, these appendages have important fitness functions such as thermoregulation, protection from physical damage, and in the case of birds, locomotion and visual communication. Although hair and feathers are defining features of mammals and birds, the placement and morphology of these structures varies widely from organism to organism. While research has identified some of the genetic mechanisms regulating formation of these appendages, little is known about the genetic and developmental mechanisms that allow their evolution. Selective breeding has produced tremendous phenotypic diversity among closely-related domestic pigeon breeds. This diversity, coupled with the experimental accessibility of their embryos, makes pigeons an powerful model for integrating evolutionary and developmental genetics. One interesting trait present in multiple breeds is the formation of head crests, whereby feathers on the back of the head have a reversed polarity, and grow forwards instead of backwards. In addition, while many pigeon breeds have scales on their feet, in a number of breeds, scales have been replaced by feathers. The proposed research will utilize domestic pigeon breeds that possess these traits to understand the genetic and developmental mechanisms that regulate epidermal appendage polarity and fate, with three aims. First, a strong candidate gene associated with crest formation will be analyzed through genetic and biochemical studies to understand its role in determining appendage polarity. Second, a candidate genomic region associated with the determination of feather vs. scale fate will be narrowed through a combination of population genomics analyses and quantitative trait locus mapping. Third, tissue recombination experiments will be used to identify how signaling interactions have changed during the evolution of foot feathering, and candidate genes identified in Aim 2 will be tested through genetic manipulation of pigeon embryos to study their role in determining epidermal organ fate. This work will integrate multiple levels of research to generate insight into how epidermal organ fate and polarity are determined, and how these traits are altered during evolution. This work also will pioneer development of the domestic pigeon as a powerful new model of vertebrate evolution and development, and will generate insights into the basis of epidermal development and disease in humans.

描述（由申请人提供）：表皮附属物的发展，例如哺乳动物的头发，羽毛和鸟类的鳞片，为研究医学上相关的过程（例如命运确定，上皮 - 间质相互作用，干细胞维持，维持干细胞维持和谱系承诺）提供了一个特别可拖延的模型。在成人生物体中，疏离附属稳态会导致癌症等疾病，强调了解如何控制发展的重要性。此外，这些附属物具有重要的健身功能，例如温度调节，免受物理损害的保护以及在鸟类的情况下，运动和视觉交流。尽管头发和羽毛定义了哺乳动物和鸟类的特征，但这些结构的位置和形态因有机体而异。尽管研究已经确定了调节这些附属形成的一些遗传机制，但对允许其进化的遗传和发育机制知之甚少。选择性育种在密切相关的家鸽子品种中产生了巨大的表型多样性。这种多样性，再加上其胚胎的实验可及性，使鸽子成为整合进化和发育遗传学的强大模型。多种品种中存在的一个有趣的特征是头冠的形成，从而使头部背面的羽毛具有反向的极性，而不是向前发展。此外，尽管许多鸽子品种的脚上有鳞片，但在许多品种中，鳞片被羽毛取代。拟议的研究将利用具有这些特征的家用鸽子品种来了解调节表皮附属物极性和命运的遗传和发育机制，并具有三个目标。首先，将通过遗传和生化研究分析与波峰形成相关的强大候选基因，以了解其在确定附属极性中的作用。其次，通过种群基因组学分析和定量性状基因座映射的结合，将范围缩小与羽毛和量表命运相关的候选基因组区域。第三，将使用组织重组实验来确定脚羽化过程中信号相互作用如何变化，而在AIM 2中鉴定出的候选基因将通过对鸽子胚胎的基因操纵来研究其在确定表皮器官命运中的作用。这项工作将整合多个级别的研究，以深入了解表皮器官的命运和极性如何确定，以及在进化过程中如何改变这些特征。这项工作还将开拓国内鸽子作为脊椎动物进化和发展的有力新模型，并将对人类表皮发展和疾病产生见解。