Enhanced expression of mouse c‐ski accompanies terminal skeletal muscle differentiation in vivo and in vitro

Abstract

Overexpression of either v-ski, or the proto-oncogene, c-ski, in quail embryo fibroblasts induces the expression of myoD and myogenin, converting the cells to myoblasts capable of differentiating into skeletal myotubes. In transgenic mice, overexpression of ski also influences muscle development, but in this case it effects fully formed muscle, causing hypertrophy of fast skeletal muscle fibers. In attempts to determine whether endogenous mouse c-ski plays a role in either early muscle cell determination or late muscle cell differentiation, we analyzed mRNA expression during muscle development in mouse embryos and during in vitro terminal differentiation of skeletal myoblasts. To generate probes for these studies we cloned coding and 3' non-coding regions of mouse c-ski. In situ hybridization revealed low c-ski expression in somites, and only detected elevated levels of mRNA in skeletal muscle beginning at about 12.5 days of gestation. Northern analysis revealed a two-fold increase in c-ski mRNA during terminal differentiation of skeletal muscle cell lines in vitro. Our results suggest that c-ski plays a role in terminal differentiation of skeletal muscle cells not in the determination of cells to the myogenic Lineage. 0 1995 Wiley-Liss, Inc.

Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial patterning, and skeletal muscle development

“…On the other hand, skiinduced myogenesis in quail fibroblasts suggested a role in both proliferation and myogenic determination (Colmenares and Stavnezer 1989). Analysis of ski expression during mouse development showed that upregulation of ski mRNA in muscle coincided with secondary myoblast proliferation (Namciu et al 1995). Our work now shows a reduction in skeletal muscle mass in ski-deficient mice, resulting from a decrease in fiber size and density.…”

“…Low levels of expression of ski mRNA have been detected in many tissues from adults in several vertebrate species Grimes et al 1993;Sleeman and Laskey 1993;Lyons et al 1994;Namciu et al 1995). In the mouse, there is a low level of expression throughout the embryo, with superimposed upregulation in specific tissues and stages.…”

Distinct molecular phenotype of malignant CD34+ hematopoietic stem and progenitor cells in chronic myelogenous leukemia

“…SKI regulates terminal differentiation of skeletal muscle (Namciu et al, 1995), and a viral homolog of SKI induced the proliferation of myeloid-erythroid multipotential progenitor cells from avian BM (Dahl et al, 1998). The SKI-induced effects in hematopoietic progenitor cells seem to be caused in part by repression of the retinoic acid receptor (RAR) signaling pathway, since high concentrations of RARa-specific ligands could revert transformation of avian progenitor cells by SKI.…”

Transforming Growth Factor-β Suppresses the Ability of Ski to Inhibit Tumor Metastasis by Inducing Its Degradation

“…Ski is expressed in almost all adult and embryonic tissues but at low levels (1,2,(22)(23)(24). Up-regulation of Ski expression occurs during certain stages of embryonic development and later in some human cancers.…”