1. Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, Illinois 60637, USA
2. Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
3. Field Museum of Natural History, Chicago, Illinois 60605, USA

Correspondence to: Neil H. Shubin^1,3 Correspondence and requests for materials should be addressed to N.H.S. (Email: nshubin@uchicago.edu).

Abstract

The genetic mechanisms regulating tetrapod limb development are well characterized, but how they were assembled during evolution and their function in basal vertebrates is poorly understood. Initial studies report that chondrichthyans, the most primitive extant vertebrates with paired appendages, differ from ray-finned fish and tetrapods in having Sonic hedgehog (Shh)-independent patterning of the appendage skeleton¹. Here we demonstrate that chondrichthyans share patterns of appendage Shh expression, Shh appendage-specific regulatory DNA, and Shh function with ray-finned fish and tetrapods^{2, 3, 4, 5, 6, 7, 8, 9, 10}. These studies demonstrate that some aspects of Shh function are deeply conserved in vertebrate phylogeny, but also highlight how the evolution of Shh regulation may underlie major morphological changes during appendage evolution.

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