The Osteoblast Transcriptome in Developing Zebrafish Reveals Key Roles for Extracellular Matrix Proteins Col10a1a and Fbln1 in Skeletal Development and Homeostasis

Zebrafish are now widely used to study skeletal development and bone-related diseases. To that end, understanding osteoblast differentiation and function, the expression of essential transcription factors, signaling molecules, and extracellular matrix proteins is crucial. We isolated Sp7-expressing...

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Published in:Biomolecules (Basel, Switzerland) Vol. 14; no. 2; p. 139
Main Authors: Raman, Ratish, Antony, Mishal, Nivelle, Renaud, Lavergne, Arnaud, Zappia, Jérémie, Guerrero-Limón, Gustavo, Caetano da Silva, Caroline, Kumari, Priyanka, Sojan, Jerry Maria, Degueldre, Christian, Bahri, Mohamed Ali, Ostertag, Agnes, Collet, Corinne, Cohen-Solal, Martine, Plenevaux, Alain, Henrotin, Yves, Renn, Jörg, Muller, Marc
Format: Journal Article Web Resource
Language:English
Published: Switzerland MDPI AG 23-01-2024
Multidisciplinary Digital Publishing Institute (MDPI)
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Summary:Zebrafish are now widely used to study skeletal development and bone-related diseases. To that end, understanding osteoblast differentiation and function, the expression of essential transcription factors, signaling molecules, and extracellular matrix proteins is crucial. We isolated Sp7-expressing osteoblasts from 4-day-old larvae using a fluorescent reporter. We identified two distinct subpopulations and characterized their specific transcriptome as well as their structural, regulatory, and signaling profile. Based on their differential expression in these subpopulations, we generated mutants for the extracellular matrix protein genes and to study their functions. The mutant larvae display reduced chondrocranium size and decreased bone mineralization, while in adults a reduced vertebral thickness and tissue mineral density, and fusion of the caudal fin vertebrae were observed. In contrast, mutants showed an increased mineralization of cranial elements and a reduced ceratohyal angle in larvae, while in adults a significantly increased vertebral centra thickness, length, volume, surface area, and tissue mineral density was observed. In addition, absence of the opercle specifically on the right side was observed. Transcriptomic analysis reveals up-regulation of genes involved in collagen biosynthesis and down-regulation of Fgf8 signaling in mutants. Taken together, our results highlight the importance of bone extracellular matrix protein genes and in skeletal development and homeostasis.
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info:eu-repo/grantAgreement/EC/H2020/766347
scopus-id:2-s2.0-85185901729
EU MSCA-ITN project
ISSN:2218-273X
2218-273X
DOI:10.3390/biom14020139