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Science 338 (6113): 1476-1480

Copyright © 2012 by the American Association for the Advancement of Science

Hox Genes Regulate Digit Patterning by Controlling the Wavelength of a Turing-Type Mechanism

Rushikesh Sheth,1,*,{dagger} Luciano Marcon,2,3,* M. Félix Bastida,1,4 Marisa Junco,1 Laura Quintana,2,3 Randall Dahn,5 Marie Kmita,6,{ddagger} James Sharpe,2,3,7,{ddagger} Maria A. Ros1,4,{ddagger}

Abstract: The formation of repetitive structures (such as stripes) in nature is often consistent with a reaction-diffusion mechanism, or Turing model, of self-organizing systems. We used mouse genetics to analyze how digit patterning (an iterative digit/nondigit pattern) is generated. We showed that the progressive reduction in Hoxa13 and Hoxd11-Hoxd13 genes (hereafter referred to as distal Hox genes) from the Gli3-null background results in progressively more severe polydactyly, displaying thinner and densely packed digits. Combined with computer modeling, our results argue for a Turing-type mechanism underlying digit patterning, in which the dose of distal Hox genes modulates the digit period or wavelength. The phenotypic similarity with fish-fin endoskeleton patterns suggests that the pentadactyl state has been achieved through modification of an ancestral Turing-type mechanism.

1 Facultad de Medicina, Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas–Sociedad para el Desarrollo Regional de Cantabria–Universidad de Cantabria, 39011 Santander, Spain.
2 European Molecular Biology Laboratory (EMBL)–Centre for Genomic Regulation (CRG) Systems Biology Research Unit, CRG, Doctor. Aiguader 88, 08003 Barcelona, Spain.
3 Universitat Pompeu Fabra, 08003 Barcelona, Spain.
4 Departamento de Anatomía y Biología Celular, Universidad de Cantabria, 39011 Santander, Spain.
5 7322 Countrywood Lane, Madison, WI 53719, USA.
6 Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Québec H2W 1R7, Canada.
7 Institució Catalana de Recerca i Estudis Avançats, Passeig Lluís Companys 23, 08010 Barcelona, Spain.

* These authors contributed equally to this work.

{dagger} Present address: Institut de Recherches Cliniques de Montréal, University of Montréal, Montréal, Québec, Canada.

{ddagger} To whom correspondence should be addressed. E-mail: marian.ros{at}unican.es (M.A.R.); james.sharpe{at}crg.eu (J.S.); marie.kmita{at}ircm.qc.ca (M.K.)


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