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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., Roehl, H.H. and Mullins, M. (2008) Regulation of Zebrafish Skeletogenesis by ext2/dackel and papst1/pinscher. PLoS Genetics, 4 (7). e1000136. ISSN 1553-7404

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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.

Item Type: Article
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.
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (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 Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Sheffield Import
Date Deposited: 30 Oct 2009 13:48
Last Modified: 08 Feb 2013 16:59
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
URI: http://eprints.whiterose.ac.uk/id/eprint/10029

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