Genetic manipulations reveal dynamic cell and gene functions: Cre-ating a new view of myogenesis.

Development of multicellular organisms is temporally and spatially complex. The Cre/loxP and Flp/FRT systems for genetic manipulation in mammals now enable researchers to explicitly examine in vivo the temporal and spatial role of cells and genes during development via cell lineage and ablation studies and conditional gene inactivation and activation. Recently we have used these methods to genetically dissect the role of Pax3(+) and Pax7(+) progenitor populations and the function of beta-catenin, an important regulator of myogenesis, in vertebrate limb myogenesis. Our lineage and ablation studies of Pax3(+) and Pax7(+) progenitors revealed surprising insights into myogenesis not apparent from Pax3 and Pax7 expression and functional studies. In addition, conditional inactivation and activation of beta-catenin in different progenitor populations and their progeny demonstrated that beta-catenin plays several cell-autonomous roles in myogenesis. Our studies highlight the hierarchical (i.e., genes versus cells), temporal and spatial complexity of development and demonstrate that manipulations of both cells and genes will be required to obtain a full understanding of the development of multicellular organisms.