Article | Published:

Developmental mechanisms of stripe patterns in rodents

Nature volume 539, pages 518523 (24 November 2016) | Download Citation


Mammalian colour patterns are among the most recognizable characteristics found in nature and can have a profound impact on fitness. However, little is known about the mechanisms underlying the formation and subsequent evolution of these patterns. Here we show that, in the African striped mouse (Rhabdomys pumilio), periodic dorsal stripes result from underlying differences in melanocyte maturation, which give rise to spatial variation in hair colour. We identify the transcription factor ALX3 as a regulator of this process. In embryonic dorsal skin, patterned expression of Alx3 precedes pigment stripes and acts to directly repress Mitf, a master regulator of melanocyte differentiation, thereby giving rise to light-coloured hair. Moreover, Alx3 is upregulated in the light stripes of chipmunks, which have independently evolved a similar dorsal pattern. Our results show a previously undescribed mechanism for modulating spatial variation in hair colour and provide insights into how phenotypic novelty evolves.

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We thank D. Mishkind, M. Omura, J. Chupasko, P. Walsh, T. Capellini, T. Linden, K. Turner and N. Hughes for providing technical and logistical support, and C. Perdomo, A. Bendesky, C. K. Hu, D. M. Kingsley and J. M. Lassance for discussions. M.Mi. and M.V. are supported by the Spanish Ministry of Economy and Competitiveness (MINECO grants BFU2011-24245 and BFU2014-52149-R) and Instituto de Salud Carlos III. CIBERDEM is an initiative of the Instituto de Salud Carlos III. H.E.H. is an Investigator of the Howard Hughes Medical Institute.

Author information


  1. Howard Hughes Medical Institute, Departments of Organismic & Evolutionary Biology and Molecular & Cellular Biology, Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA.

    • Ricardo Mallarino
    •  & Hopi E. Hoekstra
  2. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA.

    • Corneliu Henegar
    •  & Gregory S. Barsh
  3. Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.

    • Corneliu Henegar
    •  & Gregory S. Barsh
  4. Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM) and Ciber de Diabetes y Enfermedades Metabólicas Asociadas (Ciberdem), Madrid 28029, Spain.

    • Mercedes Mirasierra
    •  & Mario Vallejo
  5. Center for Interdisciplinary Research in Biology, Collège de France, Paris 75005, France.

    • Marie Manceau
  6. Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France.

    • Carsten Schradin
  7. School of Animal, Plant and Environmental Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.

    • Carsten Schradin
  8. Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

    • Slobodan Beronja


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R.M., M.Ma. and H.E.H. conceived the project. R.M., G.S.B. and H.E.H. designed experiments. R.M. performed cell proliferation assays, immunohistochemistry, quantitative PCR, in situ hybridizations, comparative sequence analysis, in vitro gain- and loss-of-function experiments and luciferase reporter assays. R.M. and M.Ma. collected samples and performed phenotypic characterization; R.M. and S.B. performed in vivo ultrasound-guided lentiviral injections. C.H. carried out the large-scale RNA experiments, including construction and annotation of the de novo transcriptome, and design and analysis of the RNA-seq work. M.Mi. and M.V. performed protein–DNA binding assays. C.S. provided the first embryos for pilot studies and founding members for the striped mice laboratory colony. R.M., G.S.B. and H.E.H. wrote the paper with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Hopi E. Hoekstra.

Reviewer Information Nature thanks H. Arnheiter, T. Caro, M. Levine and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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