Dun Color in Horses

Articles

© 2015 Nature America, Inc. All rights reserved.

Regulatory mutations in TBX3 disrupt asymmetric hair

pigmentation that underlies Dun camouflage color in horses

Freyja Imsland1,11, Kelly McGowan2,3,11, Carl-Johan Rubin1, Corneliu Henegar3, Elisabeth Sundström1,

Jonas Berglund1, Doreen Schwochow4,5, Ulla Gustafson4, Páll Imsland6, Kerstin Lindblad-Toh1,7,

Gabriella Lindgren4, Sofia Mikko4, Lee Millon8, Claire Wade7, Mikkel Schubert9, Ludovic Orlando9,

Maria Cecilia T Penedo8, Gregory S Barsh2,3 & Leif Andersson1,4,10

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.

The Dun coat color phenotype in horses is characterized by pigmentary

dilution affecting most of the body hair, leaving areas with undiluted pigment in a variable pattern, with the most common feature being a dark dorsal stripe. This stripe and other Dun pattern

elements are termed primitive markings (Fig. 1a, Online Methods

and Supplementary Fig. 1). Most domestic horses,...