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  • Oncogenomics
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Novel genes regulated by Sonic Hedgehog in pluripotent mesenchymal cells

Oncogene volume 21, pages 8196–8205 (2002)Cite this article

Abstract

Sonic Hedgehog is a secreted morphogen involved in patterning a wide range of structures in the developing embryo. Disruption of the Hedgehog signalling cascade leads to a number of developmental disorders and plays a key role in the formation of a range of human cancers. The identification of genes regulated by Hedgehog is crucial to understanding how disruption of this pathway leads to neoplastic transformation. We have used a Sonic Hedgehog (Shh) responsive mouse cell line, C3H/10T1/2, to provide a model system for hedgehog target gene discovery. Following activation of cell cultures with Shh, RNA was used to interrogate microarrays to investigate downstream transcriptional consequences of hedgehog stimulation. As a result 11 target genes have been identified, seven of which are induced (Thrombomodulin, GILZ, BF-2, Nr4a1, IGF2, PMP22, LASP1) and four of which are repressed (SFRP-1, SFRP-2, Mip1-γ, Amh) by Shh. These targets have a diverse range of putative functions and include transcriptional regulators and molecules known to be involved in regulating cell growth or apoptosis. The corroboration of genes previously implicated in hedgehog signalling, along with the finding of novel targets, demonstrates both the validity and power of the C3H/10T1/2 system for Shh target gene discovery.

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Acknowledgements

Microarray chips were a generous gift of Dr L Fowles (IMB). The pN-Myc-hGli-PRK7 construct was kindly provided by Dr F de Sauvage (Genentech Inc, San Francisco, CA, USA), whilst pShh-N-PMT21 was a kind gift of the late Dr T Yamada. Thanks to Dr T Ellis and K McCue for critical reading of the manuscript. This work was supported in part by a grant from the Australian National Health and Medical Research Council (NHMRC). The IMB incorporates the Centre for Functional and Applied Genomics, a Special Research Centre of the Australian Research Council. The Cooperative Research Centre for Discovery of Genes for Common Human Diseases is established and supported by the Australian Government's Cooperative Research Centres program. CA Wicking is an NHMRC Senior Research Fellow. WJ Ingram was supported by a Commonwealth Scholarship and Fellowship Plan (CSFP) award.

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Authors and Affiliations

  1. Institute for Molecular Bioscience, The University of Queensland, Queensland, 4072, Australia

    Wendy J Ingram, Carol A Wicking, Sean M Grimmond, Alistair R Forrest & Brandon J Wainwright

  2. Department of Biochemistry and Molecular Biology, The University of Queensland, Queensland, 4072, Australia

    Wendy J Ingram & Brandon J Wainwright

  3. Cooperative Research Centre for Discovery of Genes for Common Human Diseases, 576 Swan St, 3121, Richmond, Victoria, Australia

    Wendy J Ingram, Carol A Wicking & Brandon J Wainwright

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  1. Wendy J Ingram
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Correspondence to Brandon J Wainwright.

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Ingram, W., Wicking, C., Grimmond, S. et al. Novel genes regulated by Sonic Hedgehog in pluripotent mesenchymal cells. Oncogene 21, 8196–8205 (2002). https://doi.org/10.1038/sj.onc.1205975

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