Determining the genetic and developmental basis of epidermal appendage evolution

描述（由申请人提供）：表皮附属物的发育，如哺乳动物的毛发和鸟类的羽毛和鳞片，为研究医学相关过程（如命运决定、上皮-间充质相互作用、干细胞维持和谱系承诺）提供了一个特别容易处理的模型。在成年生物中，附属物体内平衡失调可能导致癌症等疾病，这凸显了了解发育如何被控制的重要性。此外，这些附属物具有重要的适应性功能，如体温调节、保护身体免受伤害，对鸟类来说，还具有运动和视觉交流的功能。虽然毛发和羽毛是哺乳动物和鸟类的决定性特征，但这些结构的位置和形态在不同生物之间差别很大。虽然研究已经确定了一些调节这些附属物形成的遗传机制，但对于允许它们进化的遗传和发育机制知之甚少。在亲缘关系密切的家鸽品种中，选择性育种产生了巨大的表型多样性。这种多样性，再加上它们的胚胎在实验中可获得性，使鸽子成为整合进化和发育遗传学的强大模型。在许多品种中都存在一个有趣的特征，即头冠的形成，即头部后部的羽毛具有相反的极性，并且向前而不是向后生长。此外，虽然许多鸽子品种的脚上都有鳞片，但在一些品种中，鳞片已经被羽毛所取代。本研究将利用具有这些特征的家鸽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，目的有三个。首先，将通过遗传和生化研究分析与冠形成相关的强候选基因，以了解其在决定附属物极性中的作用。其次，将通过群体基因组学分析和数量性状位点定位相结合，缩小与羽毛和鳞片命运相关的候选基因组区域。第三，组织重组实验将用于确定信号相互作用在足部羽毛进化过程中的变化，并通过对鸽子胚胎的遗传操作测试Aim 2中确定的候选基因，以研究它们在决定表皮器官命运中的作用。这项工作将整合多个层面的研究，以深入了解表皮器官的命运和极性是如何决定的，以及这些特征在进化过程中是如何改变的。这项工作还将开拓家鸽作为脊椎动物进化和发展的强大新模型的发展，并将对人类表皮发育和疾病的基础产生见解。

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 In addition, while many pigeon breeds have scales on their feet, in a number of breeds, scales have been replaced by feathers.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.