Clément, A., Wiweger, M., von der Hardt, S. et al. (5 more authors) (2008) Regulation of Zebrafish Skeletogenesis by ext2/dackel and papst1/pinscher. PLoS Genetics, 4 (7). e1000136. ISSN 1553-7404
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2008 Clément et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) > Centre for Developmental Genetics (Sheffield) The University of Sheffield > University of Sheffield Research Centres and Institutes > Centre for Developmental Genetics (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Sheffield Import |
Date Deposited: | 30 Oct 2009 13:48 |
Last Modified: | 15 Sep 2014 01:17 |
Published Version: | http://dx.doi.org/10.1371/journal.pgen.1000136 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | doi: 10.1371/journal.pgen.1000136 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:10029 |