Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses

Freyja Imsland; Kelly McGowan; Carl-Johan Rubin; Corneliu Henegar; Elisabeth Sundström; Jonas Berglund; Doreen Schwochow; Ulla Gustafson; Páll Imsland; Kerstin Lindblad-Toh; Gabriella Lindgren; Sofia Mikko; Lee Millon; Claire Wade; Mikkel Schubert; Ludovic Antoine Alexandre Orlando; Maria Cecilia T. Penedo; Gregory S. Barsh; Leif Andersson

doi:10.1038/ng.3475

Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses

Freyja Imsland, Kelly McGowan, Carl-Johan Rubin, Corneliu Henegar, Elisabeth Sundström, Jonas Berglund, Doreen Schwochow, Ulla Gustafson, Páll Imsland, Kerstin Lindblad-Toh, Gabriella Lindgren, Sofia Mikko, Lee Millon, Claire Wade, Mikkel Schubert, Ludovic Antoine Alexandre Orlando, Maria Cecilia T. Penedo, Gregory S. Barsh, Leif Andersson

34 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	48
Issue number	2
Pages (from-to)	152-158
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.3475
Publication status	Published - 1 Feb 2016

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Imsland, F., McGowan, K., Rubin, C-J., Henegar, C., Sundström, E., Berglund, J., Schwochow, D., Gustafson, U., Imsland, P., Lindblad-Toh, K., Lindgren, G., Mikko, S., Millon, L., Wade, C., Schubert, M., Orlando, L. A. A., Penedo, M. C. T., Barsh, G. S., & Andersson, L. (2016). Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses. Nature Genetics, 48(2), 152-158. https://doi.org/10.1038/ng.3475

Imsland, F, McGowan, K, Rubin, C-J, Henegar, C, Sundström, E, Berglund, J, Schwochow, D, Gustafson, U, Imsland, P, Lindblad-Toh, K, Lindgren, G, Mikko, S, Millon, L, Wade, C, Schubert, M, Orlando, LAA, Penedo, MCT, Barsh, GS & Andersson, L 2016, 'Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses', Nature Genetics, vol. 48, no. 2, pp. 152-158. https://doi.org/10.1038/ng.3475

@article{fc34a6278fc14c139d296ae41982f92b,

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.",

author = "Freyja Imsland and Kelly McGowan and Carl-Johan Rubin and Corneliu Henegar and Elisabeth Sundstr{\"o}m and Jonas Berglund and Doreen Schwochow and Ulla Gustafson and P{\'a}ll Imsland and Kerstin Lindblad-Toh and Gabriella Lindgren and Sofia Mikko and Lee Millon and Claire Wade and Mikkel Schubert and Orlando, {Ludovic Antoine Alexandre} and Penedo, {Maria Cecilia T.} and Barsh, {Gregory S.} and Leif Andersson",

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T1 - Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses

AU - Imsland, Freyja

AU - McGowan, Kelly

AU - Rubin, Carl-Johan

AU - Henegar, Corneliu

AU - Sundström, Elisabeth

AU - Berglund, Jonas

AU - Schwochow, Doreen

AU - Gustafson, Ulla

AU - Imsland, Páll

AU - Lindblad-Toh, Kerstin

AU - Lindgren, Gabriella

AU - Mikko, Sofia

AU - Millon, Lee

AU - Wade, Claire

AU - Schubert, Mikkel

AU - Orlando, Ludovic Antoine Alexandre

AU - Penedo, Maria Cecilia T.

AU - Barsh, Gregory S.

AU - Andersson, Leif

PY - 2016/2/1

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N2 - 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.

AB - 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.

U2 - 10.1038/ng.3475

DO - 10.1038/ng.3475

M3 - Journal article

C2 - 26691985

SN - 1061-4036

VL - 48

SP - 152

EP - 158

JO - Nature: New biology

JF - Nature: New biology

IS - 2

ER -

Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses

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