RRC ID 53151
著者 Letelier J, de la Calle-Mustienes E, Pieretti J, Naranjo S, Maeso I, Nakamura T, Pascual-Anaya J, Shubin NH, Schneider I, Martinez-Morales JR, Gómez-Skarmeta JL.
タイトル A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins.
ジャーナル Nat Genet
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 (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.
巻・号 50(4)
ページ 504-509
公開日 2018-4-1
DOI 10.1038/s41588-018-0080-5
PII 10.1038/s41588-018-0080-5
PMID 29556077
PMC PMC5896732
MeSH Animal Fins / growth & development* Animal Fins / metabolism* Animals Animals, Genetically Modified Body Patterning / genetics* CRISPR-Cas Systems Conserved Sequence Enhancer Elements, Genetic Evolution, Molecular Extremities / growth & development Fish Proteins / genetics Hedgehog Proteins / genetics* Humans Mice Mice, Transgenic Oryzias / genetics Oryzias / growth & development Zebrafish / genetics Zebrafish / growth & development Zebrafish Proteins / genetics
IF 27.605
引用数 15
リソース情報
メダカ ZRSdelta401 (MT1207) ZRSdelta948 (MT1208) ZRSdelta3.4kb (MT1209)