Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher.
PLoS Genet
; 4(7): e1000136, 2008 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-18654627
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Peixe-Zebra
/
N-Acetilglucosaminiltransferases
/
Regulação da Expressão Gênica no Desenvolvimento
/
Proteínas de Transporte de Ânions
/
Proteínas de Peixe-Zebra
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Reino Unido