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Título: | A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins |
Autor: | Letelier, Joaquin CSIC ORCID; Calle-Mustienes, Elisa de la CSIC ORCID; Pieretti, Joyce; Naranjo, Silvia CSIC ORCID; Maeso, Ignacio CSIC ORCID; Nakamura, Tetsuya; Pascual-Anaya, Juan; Shubin, Neil H.; Schneider, Igor; Martínez-Morales, Juan Ramón CSIC ORCID; Gómez-Skarmeta, José Luis CSIC ORCID | Palabras clave: | Developmental biology Functional genomics Gene regulation Pattern formation |
Fecha de publicación: | 2018 | Editor: | Springer Nature | Citación: | Nature Genetics 50: 504-509 (2018) | Resumen: | 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 (Oryzias latipes) ZRS and enhancer assays identify the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolishes shh expression and completely truncates 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. | Versión del editor: | http://dx.doi.org/10.1038/s41588-018-0080-5 | URI: | http://hdl.handle.net/10261/242231 | DOI: | 10.1038/s41588-018-0080-5 | ISSN: | 1061-4036 | E-ISSN: | 1546-1718 |
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