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 In addition, while many pigeon breeds have scales on their feet, in a number of breeds, scales have been replaced by feathers.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

Public Health Relevance

This study is relevant to public health because it will advance our understanding of how cell fate and tissue polarity are regulated during epidermal development, and how these processes have been altered through evolution. A better understanding of these processes could lead to techniques to promote wound healing and tissue regeneration. Also, as defects in these processes can lead to diseases such as cancer, this study could provide novel targets for disease treatment or prevention.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Hoodbhoy, Tanya
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University of Utah
Schools of Arts and Sciences
Salt Lake City
United States
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Domyan, Eric T; Kronenberg, Zev; Infante, Carlos R et al. (2016) Molecular shifts in limb identity underlie development of feathered feet in two domestic avian species. Elife 5:e12115
Kronenberg, Zev N; Osborne, Edward J; Cone, Kelsey R et al. (2015) Wham: Identifying Structural Variants of Biological Consequence. PLoS Comput Biol 11:e1004572
Vickrey, Anna I; Domyan, Eric T; Horvath, Martin P et al. (2015) Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in EphB2. Mol Biol Evol 32:2657-64
Domyan, Eric T; Guernsey, Michael W; Kronenberg, Zev et al. (2014) Epistatic and combinatorial effects of pigmentary gene mutations in the domestic pigeon. Curr Biol 24:459-64
Shapiro, Michael D; Domyan, Eric T (2013) Domestic pigeons. Curr Biol 23:R302-3