PUBLICATION
Overexpression of Notch Signaling Induces Hyperosteogeny in Zebrafish
- Authors
- Liang, S.T., Chen, J.R., Tsai, J.J., Lai, Y.H., Hsiao, C.D.
- ID
- ZDB-PUB-190729-1
- Date
- 2019
- Source
- International Journal of Molecular Sciences 20(15): (Journal)
- Registered Authors
- Hsiao, Chung-Der
- Keywords
- bone, hyperosteogeny, notch, transgenic zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Bone Diseases/genetics
- Bone Diseases/pathology
- Cell Differentiation/genetics
- Embryonic Development/genetics*
- Gene Expression Regulation, Developmental/genetics
- Homeodomain Proteins/genetics*
- Humans
- Mesenchymal Stem Cells/metabolism
- Mice
- Nerve Tissue Proteins/genetics*
- Osteoblasts/metabolism
- Osteogenesis/genetics*
- Receptor, Notch1/genetics*
- Receptors, Notch/genetics
- Signal Transduction/genetics
- Zebrafish/genetics*
- Zebrafish/growth & development
- Zebrafish Proteins/genetics*
- PubMed
- 31344827 Full text @ Int. J. Mol. Sci.
Citation
Liang, S.T., Chen, J.R., Tsai, J.J., Lai, Y.H., Hsiao, C.D. (2019) Overexpression of Notch Signaling Induces Hyperosteogeny in Zebrafish. International Journal of Molecular Sciences. 20(15).
Abstract
Notch signaling is one of the evolutionarily conserved signaling pathways in multicellular organisms. It plays an important role in embryonic development. During skeletal development of vertebrates, it regulates bone homeostasis by manipulating both osteoblastogenesis and osteoclastogenesis through different mechanisms. However, due to the different nature of Notch signaling in mesenchymal stem cell and osteoblast, regulation of Notch signaling in bone-related diseases remains unsettled. Previous studies by cell culture and mouse models showed contradictory results regarding the role of Notch signaling in bone homeostasis. To clarify the role of Notch signaling in osteogenesis, we established a zebrafish model, in which Notch1a intracellular domain (N1aICD) was specifically expressed in the osteoblasts. We found that overexpression of N1aICD in osteoblasts caused hyperosteogeny in the column region of zebrafish with the morphology of narrowed neural/hemal canals. Moreover, increased metabolic activity of osteoblasts instead of augmenting osteoblast number led to hyperosteogeny in N1aICD-overexpressed zebrafish. In summary, we successfully established a transgenic zebrafish line overexpressing N1aICD to clarify the in-vivo function of Notch signaling during osteoblastogenesis. In the future, this fish line can serve as a valuable tool to test the therapeutic drugs for hyperosteogeny.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping