Zebrafish transforming growth factor-beta-stimulated clone 22 domain 3 (TSC22D3) plays critical roles in Bmp-dependent dorsoventral patterning via 2 deubiquitinating enzymes Usp15 and Otud4
- Tse, W.K., Jiang, Y.J., and Wong, C.K.
- Biochimica et biophysica acta. General subjects 1830(10): 4584-93 (Journal)
- Registered Authors
- Jiang, Yun-Jin, Tse, Ka Fai William
- embryogenesis, osmoregulation, osmotic stress transcription factor 1
- MeSH Terms
- Amino Acid Sequence
- Base Sequence
- Body Patterning*
- Bone Morphogenetic Proteins/metabolism*
- DNA Primers
- Gene Knockdown Techniques
- Molecular Sequence Data
- Sequence Homology, Amino Acid
- Transcription Factors/chemistry
- Transcription Factors/physiology*
- Transforming Growth Factor beta/chemistry
- Transforming Growth Factor beta/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- 23665588 Full text @ BBA General Subjects
Osmotic stress transcription factor 1/transforming growth factor-β-stimulated clone 22 domain 3 (Ostf1/Tsc22d3) is a transcription factor that plays an osmoregulatory role in euryhaline fishes. Its mRNA and protein levels are up-regulated under hyperosmotic stress. However, its osmoregulatory and developmental functions have not been studied in any stenohaline freshwater fishes. Zebrafish is an excellent model to perform such study to unfold the functional role of Tsc22d3.
We identified the zebrafish Tsc22d3 and performed knockdown studies using morpholino antisense oligonucleotide (MO).
Zebrafish Tsc22d3 did not response to hypertonic stress and ts22d3 knockdown or overexpression by injecting MO or capped RNA did not change the transcriptional levels of any of the known ionocyte markers. To reveal the unknown function of zebrafish Tsc22d3, we performed several in situ molecular marker studies on tsc22d3 morphants and found that Tsc22d3 plays multi-functional roles in dorsoventral (DV) patterning, segmentation, and brain development. We then aimed to identify the mechanism of Tsc22d3 in the earliest stages of DV patterning. Our results demonstrated that tsc22d3 is a ventralized gene that can stimulate the transcription of bone morphogenetic protein 4 (bmp4) and, thus, has a positive effect on the Bmp signaling pathway. Furthermore, we showed that Tsc22d3 interacts with deubiquitinating enzymes, ubiquitin-specific protease 15 (Usp15) and ovarian tumor domain containing protein 4 (Otud4). In addition, the interruption of Bmp4 signaling by double knockdown of usp15 and otud4 reduced the ventralized effects in tsc22d3-overexpressing embryos.
This is the first study to identify new developmental functions of Tsc22d3 in zebrafish.