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The origin of skeletal muscle stem cells in the embryo and the adult Peter Bailey*, Tamara Holowacz* and Andrew B Lassar†
Skeletal muscle progenitors are specified during embryogenesis and in addition have recently been found to be generated from either mesenchymal or neural stem cells in the adult. We review recent progress in identifying the signals and transcription factors thatcontrol skeletal muscle formation during embryogenesis and in the adult.
Address Harvard Medical School, Department of Biological Chemistry and Molecular Phamacology, 240 Longwood Ave., Boston, MA 02115, USA *These authors contributed equally to this work, these names are listed alphabetically † e-mail: andrew_lassar@hms.harvard.edu † Author for correspondence Current Opinion in Cell Biology 2001,13:679–689 0955-0674/01/$ — see front matter © 2001 Elsevier Science Ltd. All rights reserved. Abbreviations bHLH basic helix-loop-helix DM dermomyotome FACS fluorescence activated cell sorting LacZ bacterial β-galactosidase gene MaSP marrow-derived SP MLC myosin light chain MPC muscle progenitor cell MuSP muscle-derived SP pRB hypophosphorylated retinoblastoma protein SCID severe combinedimmunodeficient Shh Sonic hedgehog SP side population TA tibulas anterior

Signals from surrounding tissues establish myogenic progenitors
All skeletal muscle cells, excluding those of the head, arise from the somites. The somite is a transient condensation of paraxial mesodermal cells situated adjacent to the neural tube and notochord. The somite develops into three distinct cellular compartments, thedermomyotome (DM), the myotome and the sclerotome, which in turn give rise to distinct cell fates (Figure 1). The ventromedial part of the somite responds to signals from the notochord and forms the sclerotome, which gives rise to the axial skeleton and ribs. The dorsal part of the somite responds to signals from the dorsal neural tube as well as the notochord and forms the DM and the myotome.Additional signals from the ectoderm overlying the somites can also induce DM. Cells of the DM can be identified by the expression of the paired box transcription factors Pax-3 and Pax-7 [1,2], and low level expression of the myogenic basic helix-loop-helix (bHLH) factor Myf-5 [3]. Dermomyotomal cells continue to proliferate and are maintained in an undifferentiated state by signals from the lateralplate and surface ectoderm [4,5••]. At the dorsomedial and ventrolateral lips of the DM, cells migrate under the DM to form the myotome, a sheet of differentiating skeletal muscle cells that express high levels of MyoD and Myf-5, and eventually give rise to the axial muscles [3,6,7••,8]. At the limb levels, cells in the lateral DM de-epithelialize and migrate into the limb where they will form theappendicular skeletal muscle (reviewed in [9]). Once in the limb, migratory dermomyotomal cells are influenced by local signals and initiate the skeletal muscle differentiation program. Cells from both the lateral DM and the lateral myotome migrate as a block of tissue to form the ventral body wall muscles [10,11•].

Introduction
Development of skeletal muscle in vertebrates begins during earlyembryonic stages and continues throughout an animal’s life. Multipotent cells of the embryonic mesoderm become committed to the myogenic lineage by responding to local signals from adjacent tissues. However, not all of the cells that are fated to become muscle differentiate immediately. A multitude of extrinsic and intrinsic cues temporarily restrain myogenesis, allowing proliferation of a muscleprogenitor cell (MPC) population. This leads to a prolonged recruitment of muscle tissue during embryogenesis. MPC populations are also present in adult skeletal muscle. MPCs in postnatal muscle participate in regeneration following injury and serve as the progenitors of satellite cells. Intriguingly, some of the genes that regulate the specification of the embryonic MPCs also control the...