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Conserved regulation of proximodistal limb axis development by Meis1/Hth

Author

Listed:
  • Nadia Mercader

    (Centro Nacional de Biotecnología, CSIC-UAM)

  • Esther Leonardo

    (Centro Nacional de Biotecnología, CSIC-UAM)

  • Natalia Azpiazu

    (Centro de Biología Molecular, CSIC-UAM, Universidad Autónoma de Madrid)

  • Antonio Serrano

    (Centro Nacional de Biotecnología, CSIC-UAM)

  • Ginés Morata

    (Centro de Biología Molecular, CSIC-UAM, Universidad Autónoma de Madrid)

  • Carlos Martínez-A

    (Centro Nacional de Biotecnología, CSIC-UAM)

  • Miguel Torres

    (Centro Nacional de Biotecnología, CSIC-UAM)

Abstract

Vertebrate limbs grow out from the flanks of embryos, with their main axis extending proximodistally from the trunk. Distinct limb domains, each with specific traits, are generated in a proximal-to-distal sequence during development1. Diffusible factors expressed from signalling centres promote the outgrowth of limbs and specify their dorsoventral and anteroposterior axes2,3,4. However, the molecular mechanism by which limb cells acquire their proximodistal (P–D) identity is unknown1. Here we describe the role of the homeobox genes Meis1/2 and Pbx1 in the development of mouse, chicken and Drosophila limbs. We find that Meis1/2 expression is restricted to a proximal domain, coincident with the previously reported domain in which Pbx1 is localized to the nucleus5, and resembling the distribution of the Drosophila homologues homothorax (hth)5,6 and extradenticle (exd)7; that Meis1 regulates Pbx1 activity by promoting nuclear import of the Pbx1 protein; and that ectopic expression of Meis1 in chicken and hth in Drosophila disrupts distal limb development and induces distal-to-proximal transformations. We suggest that restriction of Meis1/Hth to proximal regions of the vertebrate and insect limb is essential to specify cell fates and differentiation patterns along the P–D axis of the limb.

Suggested Citation

  • Nadia Mercader & Esther Leonardo & Natalia Azpiazu & Antonio Serrano & Ginés Morata & Carlos Martínez-A & Miguel Torres, 1999. "Conserved regulation of proximodistal limb axis development by Meis1/Hth," Nature, Nature, vol. 402(6760), pages 425-429, November.
  • Handle: RePEc:nat:nature:v:402:y:1999:i:6760:d:10.1038_46580
    DOI: 10.1038/46580
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    Cited by:

    1. Catarina R. Oliveira & Dunja Knapp & Ahmed Elewa & Tobias Gerber & Sandra G. Gonzalez Malagon & Phillip B. Gates & Hannah E. Walters & Andreas Petzold & Hernan Arce & Rodrigo C. Cordoba & Elaiyaraja S, 2022. "Tig1 regulates proximo-distal identity during salamander limb regeneration," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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