| ZFIN ID: ZDB-PUB-110128-11 |
Setdb2 restricts dorsal organizer territory and regulates left-right asymmetry through suppressing fgf8 activity
Xu, P.F., Zhu, K.Y., Jin, Y., Chen, Y., Sun, X.J., Deng, M., Chen, S.J., Chen, Z., and Liu, T.X.
| Date: | 2010 |
|---|---|
| Source: | Proceedings of the National Academy of Sciences of the United States of America 107(6): 2521-2526 (Journal) |
| Registered Authors: | Chen, Yi, Chen, Zhu, Deng, Min, Jin, Yi, Liu, Ting Xi, Sun, Xiao-Jian, Xu, Peng-Fei, Zhu, Kang-Yong |
| Keywords: | set domain, histone methylation, epigenetics, embryonic development, zebrafish |
| MeSH Terms: |
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| PubMed: | 20133783 Full text @ Proc. Natl. Acad. Sci. USA |
Citation
Xu, P.F., Zhu, K.Y., Jin, Y., Chen, Y., Sun, X.J., Deng, M., Chen, S.J., Chen, Z., and Liu, T.X. (2010) Setdb2 restricts dorsal organizer territory and regulates left-right asymmetry through suppressing fgf8 activity. Proceedings of the National Academy of Sciences of the United States of America. 107(6):2521-2526.
ABSTRACT
Dorsal organizer formation is one of the most critical steps in early embryonic development. Several genes and signaling pathways that positively regulate the dorsal organizer development have been identified; however, little is known about the factor(s) that negatively regulates the organizer formation. Here, we show that Setdb2, a SET domain-containing protein possessing potential histone H3K9 methyltransferase activity, restricts dorsal organizer development and regulates left-right asymmetry by suppressing fibroblast growth factor 8 (fgf8) expression. Knockdown of Setdb2 results in a massive expansion of dorsal organizer markers floating head (flh), goosecoid (gsc), and chordin (chd), as well as a significant increase of fgf8, but not fgf4 mRNAs. Consequently, disrupted midline patterning and resultant randomization of left-right asymmetry are observed in Setdb2-deficient embryos. These characteristic changes induced by Setdb2 deficiency can be nearly corrected by either overexpression of a dominant-negative fgf receptor or knockdown of fgf8, suggesting an essential role for Setdb2-Fgf8 signaling in restricting dorsal organizer territory and regulating left-right asymmetry. These results provide unique evidence that a SET domain-containing protein potentially involved in the epigenetic control negatively regulates dorsal organizer formation during early embryonic development.
ADDITIONAL INFORMATION
- Genes / Markers (18)
- Morpholino (3)
- Antibodies (1)
- Engineered Foreign Genes (1)
- Expression and Phenotype Data
- Mutations and Transgenics (1)
- Fish (7)
- Orthology (1)