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Title: A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
Author: Letelier, Joaquín
De La Calle-Mustienes, Elisa
Pieretti, Joyce
Naranjo, Silvia
Maeso, Ignacio
Nakamura, Tetsuya
Pascual-Anaya, Juan
Shubin, Neil H
Igor, Schneider
Martinez-Morales, Juan Ramón
Gómez-Skarmeta, José Luis
Keywords: Vertebrats
Genoma humà
Human genome
Issue Date: 2018
Publisher: Nature Publishing Group
Abstract: Despite their evolutionary, developmental, and functional importance the origin of vertebrate paired appendages remains uncertain. In mice, a single enhancer termed ZRS is solely responsible for Shh expression in limbs. Here, zebrafish and mouse transgenic assays trace the functional equivalence of ZRS across the gnathostome phylogeny. CRISPR/Cas9-mediated deletion of the medaka-ZRS and enhancer assays reveal the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolish shh expression and completely truncate pectoral fin formation. Strikingly, deletion of ZRS results in an almost complete ablation of the dorsal fin. This finding indicates that a ZRS-Shh regulatory module is shared by paired and median fins, and that paired fins likely emerged by the co‐option of developmental programs established in the median fins of stem gnathostomes. Shh function was later reinforced in pectoral fin development with the recruitment of shadow enhancers, conferring additional robustness.
Note: Versió postprint del document publicat a:
It is part of: Nature Genetics, 2018, vol. 50, num. 4, p. 504-509
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ISSN: 1061-4036
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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