PUBLICATION
Rdh10a Provides a Conserved Critical Step in the Synthesis of Retinoic Acid during Zebrafish Embryogenesis
- Authors
- D'Aniello, E., Ravisankar, P., Waxman, J.S.
- ID
- ZDB-PUB-150924-8
- Date
- 2015
- Source
- PLoS One 10: e0138588 (Journal)
- Registered Authors
- Waxman, Joshua
- Keywords
- Embryos, Zebrafish, Eyes, Animal signaling and communication, Vitamin A, Xenopus, Phenotypes, Vertebrates
- MeSH Terms
-
- Vitamin A/pharmacology
- Retinaldehyde/pharmacology
- Tretinoin/metabolism*
- Tretinoin/pharmacology
- PAX2 Transcription Factor/genetics
- PAX2 Transcription Factor/metabolism
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism*
- Body Patterning/drug effects
- Body Patterning/genetics
- Gene Knockdown Techniques
- Hot Temperature
- Alcohol Oxidoreductases/genetics
- Alcohol Oxidoreductases/metabolism*
- Animals
- Gene Expression Regulation, Developmental
- Rhombencephalon/embryology
- Rhombencephalon/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Animals, Genetically Modified
- In Situ Hybridization
- Reverse Transcriptase Polymerase Chain Reaction
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- PubMed
- 26394147 Full text @ PLoS One
Citation
D'Aniello, E., Ravisankar, P., Waxman, J.S. (2015) Rdh10a Provides a Conserved Critical Step in the Synthesis of Retinoic Acid during Zebrafish Embryogenesis. PLoS One. 10:e0138588.
Abstract
The first step in the conversion of vitamin A into retinoic acid (RA) in embryos requires retinol dehydrogenases (RDHs). Recent studies have demonstrated that RDH10 is a critical core component of the machinery that produces RA in mouse and Xenopus embryos. If the conservation of Rdh10 function in the production of RA extends to teleost embryos has not been investigated. Here, we report that zebrafish Rdh10a deficient embryos have defects consistent with loss of RA signaling, including anteriorization of the nervous system and enlarged hearts with increased cardiomyocyte number. While knockdown of Rdh10a alone produces relatively mild RA deficient phenotypes, Rdh10a can sensitize embryos to RA deficiency and enhance phenotypes observed when Aldh1a2 function is perturbed. Moreover, excess Rdh10a enhances embryonic sensitivity to retinol, which has relatively mild teratogenic effects compared to retinal and RA treatment. Performing Rdh10a regulatory expression analysis, we also demonstrate that a conserved teleost rdh10a enhancer requires Pax2 sites to drive expression in the eyes of transgenic embryos. Altogether, our results demonstrate that Rdh10a has a conserved requirement in the first step of RA production within vertebrate embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping