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  Evolution of a core gene network for skeletogenesis in chordates

Hecht, J., Stricker, S., Wiecha, U., Stiege, A., Panopoulou, G., Podsiadlowski, L., et al. (2008). Evolution of a core gene network for skeletogenesis in chordates. PLoS Genetics, 4(3), e1000025-e1000025. doi:10.1371/journal.pgen.1000025.

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Hecht, Jochen1, Author              
Stricker, Sigmar1, Author              
Wiecha, Ulrike2, Author
Stiege, Asita1, Author              
Panopoulou, Georgia3, Author              
Podsiadlowski, Lars, Author
Poustka, Albert J.3, Author              
Dieterich, Christoph, Author
Ehrich, Siegfried, Author
Suvorova, Julia1, Author              
Mundlos, Stefan1, Author              
Seitz, Volkhard1, Author              
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Max Planck Society, ou_persistent13              
3Evolution and Development (Albert Poustka), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479650              


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 Abstract: 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.


Language(s): eng - English
 Dates: 2008-03-21
 Publication Status: Published in print
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Title: PLoS Genetics
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 4 (3) Sequence Number: - Start / End Page: e1000025 - e1000025 Identifier: ISSN: 1553-7404