ZFIN ID: ZDB-PUB-080728-16
Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher
Clément, A., Wiweger, M., von der Hardt, S., Rusch, M.A., Selleck, S.B., Chien, C.B., and Roehl, H.H.
Date: 2008
Source: PLoS Genetics   4(7): e1000136 (Journal)
Registered Authors: Chien, Chi-Bin, Roehl, Henry, von der Hardt, Sophia
Keywords: Chondrocytes, Larvae, Cartilage, Zebrafish, Embryos, Bone development, Morphogenesis, Sulfates
MeSH Terms:
  • Animals
  • Anion Transport Proteins/genetics*
  • Anion Transport Proteins/physiology
  • Cloning, Molecular
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Genetic Markers
  • Homozygote
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Models, Animal
  • Mutation
  • N-Acetylglucosaminyltransferases/genetics*
  • N-Acetylglucosaminyltransferases/physiology
  • Osteogenesis/genetics*
  • Osteogenesis/physiology
  • Physical Chromosome Mapping
  • RNA, Messenger/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology
PubMed: 18654627 Full text @ PLoS Genet.
Mutations in human Exostosin genes (EXTs) confer a disease called Hereditary Multiple Exostoses (HME) that affects 1 in 50,000 among the general population. Patients with HME have a short stature and develop osteochondromas during childhood. Here we show that two zebrafish mutants, dackel (dak) and pinscher (pic), have cartilage defects that strongly resemble those seen in HME patients. We have previously determined that dak encodes zebrafish Ext2. Positional cloning of pic reveals that it encodes a sulphate transporter required for sulphation of glycans (Papst1). We show that although both dak and pic are required during cartilage morphogenesis, they are dispensable for chondrocyte and perichondral cell differentiation. They are also required for hypertrophic chondrocyte differentiation and osteoblast differentiation. Transplantation analysis indicates that dak(-/-) cells are usually rescued by neighbouring wild-type chondrocytes. In contrast, pic(-/-) chondrocytes always act autonomously and can disrupt the morphology of neighbouring wild-type cells. These findings lead to the development of a new model to explain the aetiology of HME.