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Published online 23 February 2004. doi:10.1083/jcb.200309152
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 5, 739-746
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Article

Epiblast cells that express MyoD recruit pluripotent cells to the skeletal muscle lineage



Jacquelyn Gerhart1, Christine Neely1, Benjamin Stewart1, Jordanna Perlman1, David Beckmann1, Margaretha Wallon2, Karen Knudsen2, and Mindy George-Weinstein1

1 Department of Anatomy, Philadelphia College of Osteopathic Medicine, Philadelphia, PA 19131
2 Lankenau Institute for Medical Research, Wynnewood, PA 19096

Address correspondence to Mindy George-Weinstein, Department of Anatomy, Philadelphia College of Osteopathic Medicine, 4170 City Ave., Philadelphia, PA 19131. Tel.: (215) 871-6541. Fax: (215) 871-6540. email: mindyw{at}pcom.edu

Embryonic stem cells are derived from the epiblast. A subpopulation of epiblast cells expresses MyoD mRNA and the G8 antigen in vivo. G8 positive (G8pos) and G8 negative (G8neg) populations were isolated by magnetic cell sorting. Nearly all G8pos cells switched from E- to N-cadherin and differentiated into skeletal muscle in culture. G8neg cells were impaired in their ability to switch cadherins and few formed skeletal muscle. Medium conditioned by G8pos cells stimulated skeletal myogenesis and N-cadherin synthesis in G8neg cultures. The effect of conditioned medium from G8pos cultures was inhibited by bone morphogenetic protein (BMP) 4. Treatment of G8neg cells with a soluble form of the BMP receptor-IA or Noggin promoted N-cadherin synthesis and skeletal myogenesis. These results demonstrate that MyoD-positive epiblast cells recruit pluripotent cells to the skeletal muscle lineage. The mechanism of recruitment involves blocking the BMP signaling pathway.

Key Words: embryonic stem cells; skeletal myogenesis; bone morphogenetic protein; noggin; cadherins

J. Perlman's present address is Western University of the Health Sciences, Chino Hills, CA 91709.

D. Beckmann's present address is Duke University, Durham, NC 27708.

Abbreviations used in this paper: BMP, bone morphogenetic protein; DMEM, Dulbecco's minimal essential medium; ES cell, embryonic stem cell; G8pos, G8 positive; G8neg, G8 negative; HGF/SF, hepatocyte growth factor/scatter factor; MyoDpos, MyoD positive; N-cadherinpos, N-cadherin positive.


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