PUBLICATION
A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
- Authors
- Letelier, J., de la Calle-Mustienes, E., Pieretti, J., Naranjo, S., Maeso, I., Nakamura, T., Pascual-Anaya, J., Shubin, N.H., Schneider, I., Martinez-Morales, J.R., Gómez-Skarmeta, J.L.
- ID
- ZDB-PUB-180321-24
- Date
- 2018
- Source
- Nature Genetics 50(4): 504-509 (Journal)
- Registered Authors
- de la Calle-Mustienes, Elisa, Gómez-Skarmeta, José Luis, Letelier, Joaquin, Maeso, Ignacio, Martinez-Morales, Juan R., Nakamura, Tetsuya, Naranjo, Silvia, Pieretti, Joyce, Shubin, Neil
- Keywords
- none
- MeSH Terms
-
- 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
- PubMed
- 29556077 Full text @ Nat. Genet.
Citation
Letelier, J., de la Calle-Mustienes, E., Pieretti, J., Naranjo, S., Maeso, I., Nakamura, T., Pascual-Anaya, J., Shubin, N.H., Schneider, I., Martinez-Morales, J.R., Gómez-Skarmeta, J.L. (2018) A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins. Nature Genetics. 50(4):504-509.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping