Determining the genetic and developmental basis of epidermal appendage evolution

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 In addition, while many pigeon breeds have scales on their feet, in a number of breeds, scales have been replaced by feathers.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