sec24d encoding a component of COPII is essential for vertebra formation, revealed by the analysis of the medaka...

We characterized a medaka mutant, vertebra imperfecta (vbi), that displays skeletal defects such as craniofacial malformation and delay of vertebra formation. Positional cloning analysis revealed a nonsense mutation in sec24d encoding a component of the COPII coat that plays a role in anterograde protein trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus. Immunofluorescence analysis revealed the accumulation of type II collagen in the cytoplasm of craniofacial chondrocytes, notochord cells, and the cells on the myoseptal boundary in vbi mutants. Electron microscopy analysis revealed dilation of the ER and defective secretion of ECM components from cells in both the craniofacial cartilage and notochord in vbi. The higher vertebrates have at least 4 sec24 paralogs; however, the function of each paralog in development remains unknown. sec24d is highly expressed in the tissues that are rich in extracellular matrix and is essential for the secretion of ECM component molecules leading to the formation of craniofacial cartilage and vertebra.