In the embryo and in the adult, skeletal muscle growth is dependent on the proliferation and the differentiation of muscle progenitors present within muscle masses. Despite the importance of these progenitors, their embryonic origin is unclear. Here we use electroporation of green fluorescent protein in chick somites, video confocal microscopy analysis of cell movements, and quail-chick grafting experiments to show that the dorsal compartment of the somite, the dermomyotome, is the origin of a population of muscle progenitors that contribute to the growth of trunk muscles during embryonic and fetal life. Furthermore, long-term lineage analyses indicate that satellite cells, which are known progenitors of adult skeletal muscles, derive from the same dermomyotome cell population. We conclude that embryonic muscle progenitors and satellite cells share a common origin that can be traced back to the dermomyotome.

Convergence-the independent evolution of the same trait by two or more taxa-has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels.

A regulatory mutation affecting expression of the Agouti gene shows color-specific selection in beach mice.

Myostatin, a TGF-␤ family member, is an important regulator of adult muscle size. While extensively studied in vitro, the mechanisms by which this molecule mediates its effect in vivo are poorly understood. We addressed this question using chick and mouse embryos. We show that while myostatin overexpression in chick leads to an exhaustion of the muscle progenitor population that ultimately results in muscle hypotrophy, myostatin loss of function in chick and mouse provokes an expansion of this population. Our data demonstrate that myostatin acts in vivo to regulate the balance between proliferation and differentiation of embryonic muscle progenitors by promoting their terminal differentiation through the activation of p21 and MyoD. Previous studies have suggested that myostatin imposes quiescence on muscle progenitors. Our data suggest that myostatin's effect on muscle progenitors is more complex than previously realized and is likely to be context-dependent. We propose a novel model for myostatin mode of action in vivo, in which myostatin affects the balance between proliferation and differentiation of embryonic muscle progenitors by enhancing their differentiation.[Keywords: Myostatin; skeletal muscle; embryo; p21] Supplemental material is available at http://www.genesdev.org.

The balance between stem cell self-renewal and progression into a differentiation program is of critical importance for tissue growth and regeneration. During skeletal muscle development, each muscle contains a pool of resident muscle stem cells that can either differentiate into muscle fibers or remain as proliferating progenitors. These cells express two related paired-homeobox transcription factors, Pax3 and Pax7, that are essential for ensuring the myogenic potential and survival of the progenitors (Buckingham and Relaix 2007). In the embryo, skeletal muscle is derived from transitory segmented structures called somites. Pax3/Pax7-positive muscle progenitor cells are located in the dermomyotome, which constitutes the dorsal epithelial layer of each somite. These cells enter the myotome, the first skeletal muscle to form, in the central compartment of the somite, as the dermomyotome disaggregates, from embryonic day 10.5 (E10.5) in the mouse embryo (Relaix et al. 2005). Pax3 is more extensively expressed than Pax7, initially, and Pax3 mutant embryos display somite defects with loss of the epaxial and hypaxial extremities of the dermomyotome. Muscles such as those of the limb, which normally form after delamination and migration of muscle progenitor cells from the hypaxial dermomyotome, are absent in the Pax3 mutant. Progenitor cell delamination and migration depends on c-Met (Bladt et al. 1995), which is a Pax3 target (Epstein et al. 1996;Relaix et al. 2003). As they enter myogenesis, muscle progenitor cells down-regulate Pax3 and Pax7 and activate genes for the myogenic determination factors Myf5, Mrf4, and MyoD. Subsequent muscle differentiation depends on MyoD, Mrf4, or myogenin (Buckingham 2006). During development, each forming muscle mass therefore contains a heterogeneous population of cells reflecting the multiple steps of myogenesis. The decision to enter the myogenic program or to stay undifferentiated is a crucial choice that remains poorly understood. One way to approach this process is to identify relevant Pax3 target genes. Recently it was shown that the myogenic determination gene Myf5 is a direct Pax3 target (Bajard et al. 2006). However, entry into the myogenic program and skeletal muscle differentiation must be modulated to retain the progenitor cell pool.Signaling pathways have been largely implicated in stem cell behavior. The FGF signaling pathway has been