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  • Oncogenomics
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Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling

Oncogene volume 27, pages 1489–1500 (2008)Cite this article

Abstract

Aberrant regulation of signalling mechanisms that normally orchestrate embryonic development, such as the Hedgehog, Wnt and Notch pathways, is a common feature of tumorigenesis. In order to better understand the neoplastic events mediated by Hedgehog signalling, we identified over 200 genes regulated by Sonic Hedgehog in multipotent mesodermal cells. Widespread crosstalk with other developmental signalling pathways is evident, suggesting a complex network of interactions that challenges the often over-simplistic representation of these pathways as simple linear entities. Hes1, a principal effector of the Notch pathway, was found to be a target of Sonic Hedgehog in both C3H/10T1/2 mesodermal and MNS70 neural cells. Desert Hedgehog also elicited a strong Hes1 response. While Smoothened function was found necessary for upregulation of Hes1 in response to Sonic Hedgehog, the mechanism does not require γ-secretase-mediated cleavage of Notch receptors, and appears to involve transcription factors other than RBP-Jκ. Thus, we have defined a novel mechanism for Hes1 regulation in stem-like cells that is independent of canonical Notch signalling.

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Acknowledgements

The following people kindly provided plasmids: Dr J Aster (pcDNA3-ΔE and pcDNA3-ICTX), Dr J Kitajewski (pGA981-6), Dr U Lendahl (pMIKneo-RBP(R218H)) and Dr D Solecki (pGL2-hHes1-prom-850). The MNS70 line was a gift of Dr M Nakafuku and Dr H Sasaki. D Ingram wrote software for the automated batch handling of microarray data files and provided helpful advice. Supported by the National Health and Medical Research Council of Australia, and the ARC Centre for Functional and Applied Genomics.

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Authors and Affiliations

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

    W J Ingram, K I McCue, T H Tran & B J Wainwright

  2. Department of Paediatrics and Child Health, The University of Queensland, Royal Children's Hospital, Brisbane, Queensland, Australia

    W J Ingram & A R Hallahan

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  1. W J Ingram
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Correspondence to B J Wainwright.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ingram, W., McCue, K., Tran, T. et al. Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene 27, 1489–1500 (2008). https://doi.org/10.1038/sj.onc.1210767

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