The frog Xenopus can normally regenerate its limbs at early developmental stages but loses the ability during metamorphosis. This behavior provides a potential gain-of-function model for measures that can enhance limb regeneration. Here, we show that frog limbs can be caused to form multidigit regenerates after receiving transplants of larval limb progenitor cells. It is necessary to activate Wnt/β-catenin signaling in the cells and to add Sonic hedgehog, FGF10, and thymosin β4. These factors promote survival and growth of the grafted cells and also provide pattern information. The eventual regenerates are not composed solely of donor tissue; the host cells also make a substantial contribution despite their lack of regeneration competence. Cells from adult frog legs or from regenerating tadpole tails do not promote limb regeneration, demonstrating the necessity for limb progenitor cells. These findings have obvious implications for the development of a technology to promote limb regeneration in mammals.
Bibliographical noteFunding Information:
We thank Dr. Nobuaki Kikyo and members of our laboratory for valuable scientific discussions and comments and Dr. Yasuhiko Kawakami for a critical reading of the manuscript. We thank Fang Zhou (Characterization Facility, College of Science and Engineering, University of Minnesota) for assistance with electron microscopy. This work was supported by Eureka grant R01GM088500 from the National Institute of General Medical Sciences (NIGMS).