PUBLICATION
Blocking endogenous retinoic acid degradation induces oral tooth formation in zebrafish
- Authors
- Jackman, W.R., Miranda Portillo, L.S., Cox, C.K., Ambrosio, A., Gibert, Y.
- ID
- ZDB-PUB-240307-6
- Date
- 2024
- Source
- Proceedings of the National Academy of Sciences of the United States of America 121: e2321162121e2321162121 (Journal)
- Registered Authors
- Gibert, Yann, Jackman, William (Bill)
- Keywords
- Cyp26 enzymes, Dollo's Law, cypriniforms, oral tooth, retinoic acid
- MeSH Terms
-
- Animals
- Odontogenesis
- Perciformes*
- Tooth Loss*
- Zebrafish
- PubMed
- 38446853 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Jackman, W.R., Miranda Portillo, L.S., Cox, C.K., Ambrosio, A., Gibert, Y. (2024) Blocking endogenous retinoic acid degradation induces oral tooth formation in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 121:e2321162121e2321162121.
Abstract
According to Dollo's Law of irreversibility in evolution, a lost structure is usually considered to be unable to reappear in evolution due to the accumulation over time of mutations in the genes required for its formation. Cypriniform fish are a classic model of evolutionary loss because, while they form fully operational teeth in the ventral posterior pharynx, unlike other teleosts, they do not possess oral teeth. Paleontological data show that Cypriniforms, a clade of teleost fish that includes the zebrafish, lost their oral teeth 50 to 100 Mya. In order to attempt to reverse oral tooth loss in zebrafish, we block the degradation of endogenous levels of retinoic acid (RA) using a specific inhibitor of the Cyp26 RA degrading enzymes. We demonstrate the inhibition of endogenous RA degradation is sufficient to restore oral tooth induction as marked by the re-appearance of expression of early dental mesenchyme and epithelium genes such as dlx2b and sp7 in the oral cavity. Furthermore, we show that these exogenously induced oral tooth germs are able to be at least partly calcified. Taken together, our data show that modifications of signaling pathways can have a significant effect on the reemergence of once-lost structures leading to experimentally induced reversibility of evolutionary tooth loss in cypriniforms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping