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) |