Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development

Abstract

Among extant tetrapods, salamanders are unique in showing a reversed preaxial polarity in patterning of the skeletal elements of the limbs, and in displaying the highest capacity for regeneration, including full limb and tail regeneration. These features are particularly striking as tetrapod limb development has otherwise been shown to be a highly conserved process1,2. It remains elusive whether the capacity to regenerate limbs in salamanders is mechanistically and evolutionarily linked to the aberrant pattern of limb development; both are features classically regarded as unique to urodeles3. New molecular data suggest that salamander-specific orphan genes play a central role in limb regeneration and may also be involved in the preaxial patterning during limb development4,5. Here we show that preaxial polarity in limb development was present in various groups of temnospondyl amphibians of the Carboniferous and Permian periods, including the dissorophoids Apateon and Micromelerpeton, as well as the stereospondylomorph Sclerocephalus. Limb regeneration has also been reported in Micromelerpeton6, demonstrating that both features were already present together in antecedents of modern salamanders 290 million years ago. Furthermore, data from lepospondyl ‘microsaurs’ on the amniote stem indicate that these taxa may have shown some capacity for limb regeneration and were capable of tail regeneration7, including re-patterning of the caudal vertebral column that is otherwise only seen in salamander tail regeneration. The data from fossils suggest that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are the only modern tetrapods that retained regenerative capacities as well as preaxial polarity in limb development.

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Figure 1: Phylogenetic tree depicting major groups of tetrapods.
Figure 2: Ossification patterns in the limbs of Micromelerpeton and Sclerocephalus.
Figure 3: Tail regeneration in the microsaur taxa Microbrachis and Hyloplesion in comparison with an extant salamander.

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Acknowledgements

We thank B. Ekrt, J. Müller, U. Göhlich, S. Walsh, C. Mehling, P. Barrett and R. Schoch for access to the collections under their care. H. J. Götz took the photograph in Fig. 3c; S. Lokatis took the photograph in Fig. 3b. This research was funded by an DFG Emmy Noether Grant (FR 2647/5-1) to N.B.F.; the Jackson School of Geosciences, the Banks Fellowship, Society of Vertebrate Paleontology Estes Memorial Grant and Paleontological Society Lane Student Award to J.C.O.; and the Feodor-Lynen Fellowship of the Alexander von Humboldt Foundation to F.W.

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N.B.F., C.B. and F.W. designed the research; N.B.F., C.B., J.C.O. and F.W. performed the research; N.B.F. wrote the manuscript; C.B., J.C.O. and F.W. contributed to the manuscript.

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Correspondence to Nadia B. Fröbisch.

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The authors declare no competing financial interests.

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Fröbisch, N., Bickelmann, C., Olori, J. et al. Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development. Nature 527, 231–234 (2015). https://doi.org/10.1038/nature15397

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