HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 22, 21022-21028, June 3, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/22/21022    most recent M502977200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gianakopoulos, P. J. Articles by Skerjanc, I. S. Search for Related Content PubMed PubMed Citation Articles by Gianakopoulos, P. J. Articles by Skerjanc, I. S. Social Bookmarking                      What's this?

Hedgehog Signaling Induces Cardiomyogenesis in P19 Cells^*

Peter J. Gianakopoulos and Ilona S. Skerjanc¶||

From the Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5C1, Canada and the ^¶Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada

Sonic Hedgehog (Shh) is a critical signaling factor for a variety of developmental pathways during embryogenesis, including the specification of left-right asymmetry in the heart. Mice that lack Hedgehog signaling show a delay in the induction of cardiomyogenesis, as indicated by a delayed expression of Nkx2-5. To further examine a role for Shh in cardiomyogenesis, clonal populations of P19 cells that stably express Shh, termed P19(Shh) cells, were isolated. In monolayer P19(Shh) cultures the Shh pathway was functional as shown by the up-regulation of Ptc1 and Gli1 expression, but no cardiac muscle markers were activated. However, Shh expression induced cardiomyogenesis following cellular aggregation, resulting in the expression of factors expressed in cardiac muscle including GATA-4, MEF2C, and Nkx2-5. Furthermore, aggregated P19 cell lines expressing Gli2 or Meox1 also up-regulated the expression of cardiac muscle factors, leading to cardiomyogenesis. Meox1 up-regulated the expression of Gli1 and Gli2 and, thus, can modify the Shh signaling pathway. Finally, Shh, Gli2, and Meox1 all up-regulated BMP-4 expression, implying that activation of the Hedgehog pathway can regulate bone morphogenetic protein signals. Taken together, we propose a model in which Shh, functioning via Gli1/2, can specify mesodermal cells into the cardiac muscle lineage.

Received for publication, March 17, 2005

^* This work was supported in part by Canadian Institutes of Health Research Grant FRN 53277 (to I. S. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a Premier's Research Excellence Award in partnership with the Foundation for Gene and Cell Therapy and an Ontario Graduate Scholarships in Science and Technology award.

^|| Supported by a Canadian Institute of Aging Investigator Award. To whom correspondence should be addressed: Dept. of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Rd., Ottawa, Ontario K1H 8M5, Canada. Tel.: 613-562-5800 ext. 8669; Fax: 613-562-5452; E-mail: iskerjan{at}uottawa.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. A. Thomas, M. Koudijs, F. J. M. van Eeden, A. L. Joyner, and D. Yelon Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential Development, November 15, 2008; 135(22): 3789 - 3799. [Abstract] [Full Text] [PDF]

				J. Synnergren, K. Akesson, K. Dahlenborg, H. Vidarsson, C. Ameen, D. Steel, A. Lindahl, B. Olsson, and P. Sartipy Molecular Signature of Cardiomyocyte Clusters Derived from Human Embryonic Stem Cells Stem Cells, July 1, 2008; 26(7): 1831 - 1840. [Abstract] [Full Text] [PDF]

				M. Wagner and M. A. Q. Siddiqui Signal Transduction in Early Heart Development (I): Cardiogenic Induction and Heart Tube Formation Experimental Biology and Medicine, July 1, 2007; 232(7): 852 - 865. [Abstract] [Full Text] [PDF]

				Z. Yang, Y. Sui, S. Xiong, S. S. Liour, A. C. Phillips, and L. Ko Switched alternative splicing of oncogene CoAA during embryonal carcinoma stem cell differentiation Nucleic Acids Res., March 4, 2007; 35(6): 1919 - 1932. [Abstract] [Full Text] [PDF]

				M. F. Bijlsma, M. P. Peppelenbosch, and C. A. Spek Hedgehog Morphogen in Cardiovascular Disease Circulation, October 31, 2006; 114(18): 1985 - 1991. [Abstract] [Full Text] [PDF]

				C. Karamboulas, A. Swedani, C. Ward, A. S. Al-Madhoun, S. Wilton, S. Boisvenue, A. G. Ridgeway, and I. S. Skerjanc HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage J. Cell Sci., October 15, 2006; 119(20): 4305 - 4314. [Abstract] [Full Text] [PDF]

				A. R. Meloni, G. B. Fralish, P. Kelly, A. Salahpour, J. K. Chen, R. J. Wechsler-Reya, R. J. Lefkowitz, and M. G. Caron Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2 Mol. Cell. Biol., October 15, 2006; 26(20): 7550 - 7560. [Abstract] [Full Text] [PDF]

				C. Karamboulas, G. D. Dakubo, J. Liu, Y. De Repentigny, K. Yutzey, V. A. Wallace, R. Kothary, and I. S. Skerjanc Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis J. Cell Sci., October 15, 2006; 119(20): 4315 - 4321. [Abstract] [Full Text] [PDF]