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First published online 17 August 2005
doi: 10.1242/dev.01976

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Proximodistal identity during vertebrate limb regeneration is regulated by Meis homeodomain proteins

Nadia Mercader^1,*, Elly M. Tanaka² and Miguel Torres^1,

¹ Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, E-28049 Madrid, Spain
² Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauer Strasse 108, 01307 Dresden, Germany

Author for correspondence (e-mail: mtorres{at}cnb.uam.es)

Accepted 11 July 2005

The mechanisms by which cells obtain instructions to precisely re-create the missing parts of an organ remain an unresolved question in regenerative biology. Urodele limb regeneration is a powerful model in which to study these mechanisms. Following limb amputation, blastema cells interpret the proximal-most positional identity in the stump to reproduce missing parts faithfully. Classical experiments showed the ability of retinoic acid (RA) to proximalize blastema positional values. Meis homeobox genes are involved in RA-dependent specification of proximal cell identity during limb development. To understand the molecular basis for specifying proximal positional identities during regeneration, we isolated the axolotl Meis homeobox family. Axolotl Meis genes are RA-regulated during both regeneration and embryonic limb development. During limb regeneration, Meis overexpression relocates distal blastema cells to more proximal locations, whereas Meis knockdown inhibits RA proximalization of limb blastemas. Meis genes are thus crucial targets of RA proximalizing activity on blastema cells.

Key words: Axolotl, Retinoic acid, Vitamin A, Homeobox

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