Overexpression of Notch Signaling Induces Hyperosteogeny in Zebrafish

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jul 27

PMID 31344827

Citations 4

Authors

Sung-Tzu Liang

Jung-Ren Chen

Jhih-Jie Tsai

Yu-Heng Lai

Chung-Der Hsiao

Affiliations

Soon will be listed here.

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.

Citing Articles

Metabolomics in Bone Research.

Fan J, Jahed V, Klavins K Metabolites. 2021; 11(7).

PMID: 34357328 PMC: 8303949. DOI: 10.3390/metabo11070434.

Signaling network regulating osteogenesis in mesenchymal stem cells.

Thomas S, Jaganathan B J Cell Commun Signal. 2021; 16(1):47-61.

PMID: 34236594 PMC: 8688675. DOI: 10.1007/s12079-021-00635-1.

Weak genetic signal for phenotypic integration implicates developmental processes as major regulators of trait covariation.

Conith A, Hope S, Chhouk B, Albertson R Mol Ecol. 2020; 30(2):464-480.

PMID: 33231336 PMC: 8811731. DOI: 10.1111/mec.15748.

Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders.

Tonelli F, Bek J, Besio R, De Clercq A, Leoni L, Salmon P Front Endocrinol (Lausanne). 2020; 11:489.

PMID: 32849280 PMC: 7416647. DOI: 10.3389/fendo.2020.00489.

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