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.In vertebrates endochondral bone formation involves first the formation of cartilage primordia, followed by its replacement by bone. This process is associated with several changes in the differentiation status of chondrocytes in the growth plate and results in a modification of the extracellular matrix composition. The cartilage matrix contains predominantly type II collagen. During endochondral ossification, chondrocytes enter a process of maturation characterized by cellular hypertrophy, a decrease in type II collagen expression, and the onset in type X collagen expression. After full differentiation of hypertrophic chondrocytes the cartilage matrix calcifies. Ossification begins with the invasion of the calcified cartilage by blood capillaries. This neo-vascularization of the growth plate is concomitant with apoptosis of most hypertrophic chondrocytes. The resulting cartilage matrix provides a scaffold for osteoblasts, which invade the cartilage mold, along with blood vessels, so laying down a bone matrix characterized by the presence of osteocalcin (reviewed in Ref.