Long-Chain Acyl-CoA Synthetase 4A Regulates Smad Activity and Dorsoventral Patterning in the Zebrafish Embryo
- Authors
- Miyares, R.L., Stein, C., Renisch, B., Anderson, J.L., Hammerschmidt, M., and Farber, S.A.
- ID
- ZDB-PUB-140210-23
- Date
- 2013
- Source
- Developmental Cell 27(6): 635-647 (Journal)
- Registered Authors
- Anderson, Jennifer, Anderson, Jennifer, Farber, Steven, Hammerschmidt, Matthias, Miyares, Rosa, Renisch, Bjoern, Stein, Cornelia
- Keywords
- none
- MeSH Terms
-
- Glycogen Synthase Kinase 3/genetics
- Glycogen Synthase Kinase 3/metabolism
- Molecular Sequence Data
- Phenotype
- Animals
- Sequence Homology, Amino Acid
- Amino Acid Sequence
- Fatty Acids, Unsaturated/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Acyl Coenzyme A/metabolism
- Phosphorylation
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- p38 Mitogen-Activated Protein Kinases/genetics
- p38 Mitogen-Activated Protein Kinases/metabolism
- In Situ Hybridization
- Signal Transduction
- Bone Morphogenetic Proteins/genetics
- Bone Morphogenetic Proteins/metabolism
- Body Patterning/physiology*
- Smad Proteins, Receptor-Regulated/genetics
- Smad Proteins, Receptor-Regulated/metabolism
- Transforming Growth Factor beta/genetics
- Transforming Growth Factor beta/metabolism
- Blotting, Western
- Coenzyme A Ligases/genetics
- Coenzyme A Ligases/metabolism
- Gene Expression Regulation, Developmental*
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism*
- PubMed
- 24332754 Full text @ Dev. Cell
Long-chain polyunsaturated fatty acids (LC-PUFA) and their metabolites are critical players in cell biology and embryonic development. Here we show that long-chain acyl-CoA synthetase 4a (Acsl4a), an LC-PUFA activating enzyme, is essential for proper patterning of the zebrafish dorsoventral axis. Loss of Acsl4a results in dorsalized embryos due to attenuated bone morphogenetic protein (Bmp) signaling. We demonstrate that Acsl4a modulates the activity of Smad transcription factors, the downstream mediators of Bmp signaling. Acsl4a promotes the inhibition of p38 mitogen-activated protein kinase and the Akt-mediated inhibition of glycogen synthase kinase 3, critical inhibitors of Smad activity. Consequently, introduction of a constitutively active Akt can rescue the dorsalized phenotype of Acsl4a-deficient embryos. Our results reveal a critical role for Acsl4a in modulating Bmp-Smad activity and provide a potential avenue for LC-PUFAs to influence a variety of developmental processes.