Conserved regulation of proximodistal limb axis development by Meis1/Hth.

Mercader Huber, Nadia; Leonardo, E; Azpiazu, N; Serrano, A; Morata, G; Martínez, C; Torres, M (1999). Conserved regulation of proximodistal limb axis development by Meis1/Hth. Nature, 402(6760), pp. 425-429. Macmillan Journals Ltd. 10.1038/46580

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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 development. Diffusible factors expressed from signalling centres promote the outgrowth of limbs and specify their dorsoventral and anteroposterior axes. However, the molecular mechanism by which limb cells acquire their proximodistal (P-D) identity is unknown. 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 nucleus, and resembling the distribution of the Drosophila homologues homothorax (hth) and extradenticle (exd); 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Mercader Huber, Nadia Isabel


600 Technology > 610 Medicine & health




Macmillan Journals Ltd.




Nadia Isabel Mercader Huber

Date Deposited:

28 Apr 2016 09:36

Last Modified:

02 Mar 2023 23:27

Publisher DOI:


PubMed ID:



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