PUBLICATION
Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish
- Authors
- Gouttenoire, J., Valcourt, U., Bougault, C., Aubert-Foucher, E., Arnaud, E., Giraud, L., and Mallein-Gerin, F.
- ID
- ZDB-PUB-070907-7
- Date
- 2007
- Source
- The Journal of biological chemistry 282(42): 30960-30973 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Transforming Growth Factor beta/pharmacology
- Caenorhabditis elegans/embryology
- Caenorhabditis elegans/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Chlamydomonas reinhardtii/genetics
- Chlamydomonas reinhardtii/metabolism
- Chondrocytes/cytology
- Chondrocytes/metabolism*
- Bone Morphogenetic Protein 2
- Chondrogenesis/drug effects
- Chondrogenesis/physiology*
- Animals
- Bone Morphogenetic Proteins/pharmacology
- Intracellular Signaling Peptides and Proteins/antagonists & inhibitors
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism*
- Growth Plate/cytology
- Growth Plate/embryology*
- Sequence Homology, Amino Acid
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Cilia/genetics
- Cilia/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/physiology*
- Humans
- RNA, Small Interfering/genetics
- RNA, Small Interfering/pharmacology
- Caenorhabditis elegans Proteins/antagonists & inhibitors
- Caenorhabditis elegans Proteins/genetics
- Caenorhabditis elegans Proteins/metabolism
- Mice
- Cartilage/embryology*
- Oligonucleotides, Antisense/genetics
- Oligonucleotides, Antisense/pharmacology
- Protozoan Proteins/antagonists & inhibitors
- Protozoan Proteins/genetics
- Protozoan Proteins/metabolism
- PubMed
- 17720815 Full text @ J. Biol. Chem.
Citation
Gouttenoire, J., Valcourt, U., Bougault, C., Aubert-Foucher, E., Arnaud, E., Giraud, L., and Mallein-Gerin, F. (2007) Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish. The Journal of biological chemistry. 282(42):30960-30973.
Abstract
Bone Morphogenetic Proteins (BMPs) act as multifunctional regulators in morphogenesis during development. In particular they play a determinant role in the formation of cartilage moulds and their transformation into 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 (siRNA) 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping