Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish.

Détails

ID Serval
serval:BIB_15006ED2FDE5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish.
Périodique
Journal of Biological Chemistry
Auteur(s)
Gouttenoire J., Valcourt U., Bougault C., Aubert-Foucher E., Arnaud E., Giraud L., Mallein-Gerin F.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2007
Volume
282
Numéro
42
Pages
30960-30973
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Bone morphogenetic proteins (BMPs) act as multifunctional regulators in morphogenesis during development. In particular they play a determinant role in the formation of cartilage molds and their replacement by bone during endochondral ossification. In cell culture, BMP-2 favors chondrogenic expression and promotes hypertrophic maturation of chondrocytes. In mouse chondrocytes we have identified a BMP-2-sensitive gene encoding a protein of 301 amino acids. This protein, named mIFT46, is the mouse ortholog of recently identified Caenorhabditis elegans and Chlamydomonas reinhardtii intraflagellar transport (IFT) proteins. After generation of a polyclonal antibody against mIFT46, we showed for the first time that the endogenous protein is located in the primary cilium of chondrocytes. We also found that mIFT46 is preferentially expressed in early hypertrophic chondrocytes located in the growth plate. Additionally, mIFT46 knockdown by small interfering RNA oligonucleotides in cultured chondrocytes specifically stimulated the expression of several genes related to skeletogenesis. Furthermore, Northern blotting analysis indicated that mIFT46 is also expressed before chondrogenesis in embryonic mouse development, suggesting that the role of mIFT46 might not be restricted to cartilage. To explore the role of IFT46 during early development, we injected antisense morpholino oligonucleotides in Danio rerio embryos to reduce zebrafish IFT46 protein (zIFT46) synthesis. Dramatic defects in embryonic development such as a dorsalization and a tail duplication were observed. Thus our results taken together indicate that the ciliary protein IFT46 has a specific function in chondrocytes and is also essential for normal development of vertebrates.
Mots-clé
Animals, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins/pharmacology, Caenorhabditis elegans/embryology, Caenorhabditis elegans/genetics, Caenorhabditis elegans Proteins/antagonists & inhibitors, Caenorhabditis elegans Proteins/genetics, Cartilage/embryology, Chlamydomonas reinhardtii/genetics, Chlamydomonas reinhardtii/metabolism, Chondrocytes/cytology, Chondrocytes/metabolism, Chondrogenesis/drug effects, Chondrogenesis/physiology, Cilia/genetics, Cilia/metabolism, Gene Expression Regulation, Developmental/drug effects, Gene Expression Regulation, Developmental/physiology, Growth Plate/cytology, Growth Plate/embryology, Humans, Intracellular Signaling Peptides and Proteins/antagonists & inhibitors, Intracellular Signaling Peptides and Proteins/genetics, Mice, Oligonucleotides, Antisense/genetics, Oligonucleotides, Antisense/pharmacology, Protozoan Proteins/antagonists & inhibitors, Protozoan Proteins/genetics, RNA, Small Interfering/genetics, RNA, Small Interfering/pharmacology, Sequence Homology, Amino Acid, Transforming Growth Factor beta/pharmacology, Zebrafish/embryology, Zebrafish/genetics, Zebrafish Proteins/antagonists & inhibitors, Zebrafish Proteins/genetics
Pubmed
Open Access
Oui
Création de la notice
01/10/2015 15:30
Dernière modification de la notice
20/08/2019 12:43
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