A. Herwig

University of Göttingen

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Heidi Hahn

Universitätsmedizin Göttingen

Roland Kappler

Ludwig-Maximilians-Universität München

M. Koleva

Bulgarian Academy of Sciences

Milena Koleva

University of Göttingen

U. Heinzmann

Bielefeld University

Jerzy Adamski

Helmholtz Zentrum München

Udo Schnitzbauer

University of Zurich

Florian Graedler

Helmholtz Zentrum München

Leticia Quintanilla‐Martinez

Universitätsklinikum Tübingen

Julia Calzada‐Wack

Helmholtz Zentrum München

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Technical University of Munich

Helmholtz Zentrum München

Institute of Groundwater Ecology

Klinikum rechts der Isar

Ludwig-Maximilians-Universität München

University of Göttingen

Center for Environmental Health

German Cancer Research Center

Deutschen Konsortium für Translationale Krebsforschung

Goethe University Frankfurt

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Research Article Pleiotropic effects of sonic hedgehog on muscle satellite cells

M. Koleva Roland Kappler A. Herwig Heidi Hahn

Muscle satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. A regu- latory disruption of growth and differentiation of these cells is assumed to result in tumor formation. Here we provide for the first time evidence that sonic hedgehog (Shh) regulates the cell fate of adult muscle satellite cells in mammals. Shh promotes cell division of satellite cells (and of the related model C2C12 cells) and prevents their differentiation into multinucleated myotubes. In addition, Shh inhibits caspase-3 activation and apoptosis induced by serum deprivation. These effects of Shh are reversed by simultaneous administration of cyclopamine, a specific inhibitor of the Shh pathway. Taken together, Shh acts as a proliferation and survival factor of satellite cells in the adult muscle. Our results support the hypothesis of the rhabdomyosarcoma origin from satellite cells and suggest a role for Shh in this process.

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Multinucleate

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Molecular characterization of Patched‐associated rhabdomyosarcoma

The Journal of Pathology (2003)

Roland Kappler Julia Calzada‐Wack Udo Schnitzbauer Milena Koleva A. Herwig

Abstract Mutations in the human homologue of Drosophila Patched1 ( PTCH1 ) have been found in several common tumours including basal cell carcinoma, medulloblastoma, and rhabdomyosarcoma (RMS). Medulloblastoma and RMS are also present in the murine model for Ptch1 deficiency. Tumours in heterozygous Ptch1 neo 67/+ mice consistently exhibit elevated transcript levels of the proto‐oncogene Gli1 , of Ptch1 itself, and of the insulin‐like growth factor 2 ( Igf2 ). The present study has investigated additional molecular changes in RMSs of Ptch1 mutant mice by means of microarray analysis and protein expression analysis. The data show activation of the cell survival‐promoting Akt/protein kinase B (Pkb). Furthermore, RMSs express increased levels of the anti‐apoptotic protein Bcl‐2 and of genes and proteins known to inhibit cell proliferation, including Gadd45a and p27 kip1 . Taken together, the data suggest that the formation of RMSs in Ptch1 mutants is associated with the ability of tumour cells to resist apoptosis. Copyright © 2003 John Wiley & Sons, Ltd.

PTCH1

GLI1

10.1002/path.1361

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Pleiotropic effects of sonic hedgehog on muscle satellite cells

Cellular and Molecular Life Sciences (2005)

M. Koleva Roland Kappler Meike Vogler A. Herwig Simone Fulda

Cyclopamine

Multinucleate

10.1007/s00018-005-5072-9

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Citations (75)