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Science 314 (5804): 1447-1450

Copyright © 2006 by the American Association for the Advancement of Science

WNT and DKK Determine Hair Follicle Spacing Through a Reaction-Diffusion Mechanism

Stefanie Sick,1 Stefan Reinker,2* Jens Timmer,2 Thomas Schlake1{dagger}

Abstract: Mathematical reaction-diffusion models have been suggested to describe formation of animal pigmentation patterns and distribution of epidermal appendages. However, the crucial signals and in vivo mechanisms are still elusive. Here we identify WNT and its inhibitor DKK as primary determinants of murine hair follicle spacing, using a combined experimental and computational modeling approach. Transgenic DKK overexpression reduces overall appendage density. Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program. These results confirm predictions of a WNT/DKK-specific mathematical model and provide in vivo corroboration of the reaction-diffusion mechanism for epidermal appendage formation.

1 Max-Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
2 Institut für Physik, Universität Freiburg, Hermann-Herder-Strasse 3, 79104 Freiburg, Germany.

* Present address: Novartis Institutes for Biomedical Research, Basel, Switzerland.

{dagger} To whom correspondence should be addressed. E-mail: schlake{at}

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