title: Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses.
abstract: Dun is a wild-type coat color in horses characterized by pigment dilution with a striking pattern of dark areas termed primitive markings. Here we show that pigment dilution in Dun horses is due to radially asymmetric deposition of pigment in the growing hair caused by localized expression of the T-box 3 (TBX3) transcription factor in hair follicles, which in turn determines the distribution of hair follicle melanocytes. Most domestic horses are non-dun, a more intensely pigmented phenotype caused by regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs. We identified two different alleles (non-dun1 and non-dun2) causing non-dun color. non-dun2 is a recently derived allele, whereas the Dun and non-dun1 alleles are found in ancient horse DNA, demonstrating that this polymorphism predates horse domestication. These findings uncover a new developmental role for T-box genes and new aspects of hair follicle biology and pigmentation.
authors.affiliation: Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Freyja
authors.initials: F
authors.lastname: Imsland
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.|Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: McGowan
authors.affiliation: Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Rubin
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Corneliu
authors.initials: C
authors.lastname: Henegar
authors.affiliation: Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sundström
authors.affiliation: Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Berglund
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.|Institut National de la Recherche Agronomique (INRA), AgroParisTech, Génetique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Doreen
authors.initials: D
authors.lastname: Schwochow
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Gustafson
authors.affiliation: Menntaskólinn við Hamrahlíð, Reykjavík, Iceland.
authors.forename: Páll
authors.initials: P
authors.lastname: Imsland
authors.affiliation: Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lindgren
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mikko
authors.affiliation: Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Millon
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Claire
authors.identifier: http://orcid.org/0000-0003-3413-4771
authors.initials: C
authors.lastname: Wade
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Schubert
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Orlando
authors.affiliation: Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Maria Cecilia T
authors.initials: MC
authors.lastname: Penedo
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.|Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
authors.affiliation: Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.|Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.|Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
authors.forename: Leif
authors.initials: L
authors.lastname: Andersson
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006200:Hair Color / Q000235:genetics*; D018859:Hair Follicle / Q000378:metabolism; D006736:Horses / Q000235:genetics*; D009154:Mutation; D012867:Skin / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins