Modification of mitochondrial metabolism in fibroblasts from mice with a skeletal muscle mutation (muscular dysgenesis) - Evidence of embryonic communication between myoblasts and fibroblasts

Muscle development during embryogenesis is a complex process involving many mechanisms. It requires a close communication among the different cellular types of the muscle, especially the fibroblasts and myoblasts. Indeed, any abnormality in one cell type might influence the differentiation of the ot her. Thus, any disturbance altering the metabolism of the myoblasts might l ead to modifications in the fibroblasts. To study this phenomenon, we used the dysgenic mouse (mdg-"muscular dysgenesis") carrying a homozygous recess ive lethal mutation expressed only in skeletal muscle cells. First, we foun d that fibroblasts isolated from such mutant muscle (and not from mutant sk in tissue) and grown in culture exhibited an altered metabolism. Secondly, muscle fibroblasts showed a lower capacity for proliferation. We also obser ved that respiration and ATP synthesis of dysgenic muscle fibroblasts were deficient, while respiratory chain enzymatic activities were normal. Finall y, intracellular [Ca2+] levels of dysgenic fibroblasts are 50% of those of normal fibroblasts. These results support the hypothesis that certain chara cteristics of fibroblasts are determined by the surrounding cellular enviro nment during embryonic organogenesis, and that such modifications are stabl e when the fibroblasts are isolated in vitro. Since fibroblast differentiat ion was disrupted permanently, this suggests, in the case of myopathies, th at the modified cells, surrounding the muscle tissue, could contribute to t he muscle pathology. Synergistic activities of this type should be consider ed when studying the course of pathologies in different types of muscle dis eases.