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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 408448.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Evolution of a core gene network for skeletogenesis in chordates
Authors:Hecht, Jochen; Stricker, Sigmar; Wiecha, Ulrike; Stiege, Asita; Panopoulou, Georgia; Podsiadlowski, Lars; Poustka, Albert J.; Dieterich, Christoph; Ehrich, Siegfried; Suvorova, Julia; Mundlos, Stefan; Seitz, Volkhard
Date of Publication (YYYY-MM-DD):2008-03-21
Title of Journal:PLoS Genetics
Issue / Number:3
Start Page:e1000025
End Page:e1000025
Copyright:© 2008 Hecht 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 author and source are credited.
Review Status:not specified
Audience:Experts Only
Abstract / Description:The skeleton is one of the most important features for the reconstruction of vertebrate phylogeny but few data are available to understand its molecular origin. In mammals the Runt genes are central regulators of skeletogenesis. Runx2 was shown to be essential for osteoblast differentiation, tooth development, and bone formation. Both Runx2 and Runx3 are essential for chondrocyte maturation. Furthermore, Runx2 directly regulates Indian hedgehog expression, a master coordinator of skeletal development. To clarify the correlation of Runt gene evolution and the emergence of cartilage and bone in vertebrates, we cloned the Runt genes from hagfish as representative of jawless fish (MgRunxA, MgRunxB) and from dogfish as representative of jawed cartilaginous fish (ScRunx1–3). According to our phylogenetic reconstruction the stem species of chordates harboured a single Runt gene and thereafter Runt locus duplications occurred during early vertebrate evolution. All newly isolated Runt genes were expressed in cartilage according to quantitative PCR. In situ hybridisation confirmed high MgRunxA expression in hard cartilage of hagfish. In dogfish ScRunx2 and ScRunx3 were expressed in embryonal cartilage whereas all three Runt genes were detected in teeth and placoid scales. In cephalochordates (lancelets) Runt, Hedgehog and SoxE were strongly expressed in the gill bars and expression of Runt and Hedgehog was found in endo- as well as ectodermal cells. Furthermore we demonstrate that the lancelet Runt protein binds to Runt binding sites in the lancelet Hedgehog promoter and regulates its activity. Together, these results suggest that Runt and Hedgehog were part of a core gene network for cartilage formation, which was already active in the gill bars of the common ancestor of cephalochordates and vertebrates and diversified after Runt duplications had occurred during vertebrate evolution. The similarities in expression patterns of Runt genes support the view that teeth and placoid scales evolved from a homologous developmental module.
Comment of the Author/Creator:E-mail:
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:BCRT, Universitätsmedizin Charité, Berlin, Germany Department of Animal Systematics and Evolution, Free University, Berlin, Germany
MPI for Developmental Biology Department 4 - Evolutionary Biology, Tübingen, Germany
Bundesforschungsanstalt für Fischerei, Hamburg, Germany
Institute for Medical Genetics, Charité, Universitätsmedizin Berlin, Berlin, Germany
Identifiers:ISSN:1553-7404 [eISSN]
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