CYTOSKELETAL CONTROL OF MYOGENESIS - A DESMIN NULL MUTATION BLOCKS THE MYOGENIC PATHWAY DURING EMBRYONIC STEM-CELL DIFFERENTIATION

A differentiating system based on embryonic stem (ES) cell-derived emb ryoid bodies (EBs) which recapitulates the in vivo cardiac, skeletal, and smooth muscle myogenesis of mouse embryos was developed and used t o investigate the effects of the disruption of the desmin gene on musc le cell differentiation. Wild-type, heterozygous, and homozygous cell lines with the mutated desmin allele were evaluated. Skeletal myogenes is Tvas totally inhibited in desmin null mutant EBs, as manifested by the absence of myotube formation, contractility, and myoD, myogenin, m yf5, and myosin heavy chain expression. Smooth muscle formation was al so completely blocked in the absence of desmin, On the other hand, the re were no obvious effects on cardiomyocyte differentiation in these d esmin null mutant EBs. However, reduced desmin expression in EBs heter ozygous for the desmin mutation leads to partial inhibition of cardiac muscle formation. These data suggest that in contrast to early cardio cyte differentiation, desmin is indispensable for skeletal and smooth muscle formation. (C) 1995 Academic Press, Inc.