Review

Proximal to distal patterning during limb development and regeneration: a review of converging disciplines

Francesca V Mariani

Eli & Edythe Broad Center for Regenerative Medicine & Stem Cell Research, Keck School of Medicine, University of Southern California, 1450 Biggy Street, NRT-4505, Los Angeles, CA 90033-9601, USA.

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Email the corresponding author at fmariani@usc.edu

Published Online:10 May 2010https://doi.org/10.2217/rme.10.27

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Abstract

Regeneration of lost structures typically involves distinct events: wound healing at the damaged site, the accumulation of cells that will be used as future building blocks and, finally, the initiation of molecular signaling pathways that dictate the form and pattern of the regenerated structures. Amphibians and urodeles in particular, have long been known to have exceptional regenerative properties. For many years, these animals have been the model of choice for understanding limb regeneration, a complex process that involves reconstructing skin, muscle, bone, connective tissue and nerves into a functional 3D structure. It appears that this process of rebuilding an adult limb has many similarities with how the limb forms in the first place – for example, in the embryo, all the components of the limb need to be formed and this requires signaling mechanisms to specify the final pattern. Thus, both limb formation and limb regeneration are likely to employ the same molecular pathways. Given the available tools of molecular biology and genetics, this is an exciting time for both fields to share findings and make significant progress in understanding more about the events that dictate embryonic limb pattern and control limb regeneration. This article focuses particularly on what is known about the molecular control of patterning along the proximal–distal axis.

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Published online 10 May 2010

Published in print May 2010

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Acknowledgements

The author wishes to thank Gail Martin, Elly Tanaka, David Gardiner, members of her laboratory and several anonymous reviewers for helpful suggestions and discussions. Some of the themes in this review have also been discussed by others, and the author regrets that it was not possible to cite all of the relevant literature due to space constraints.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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