During myogenesis, induction of muscle-specific genes is subject to negative control by polypeptide mitogens and type-13 transforming growth factor. Since transduction of growth factor signals may require proteins encoded by cellular ras oncogenes, we have tested whether a mutationally altered Harvey ras expression vector, by itself, can prevent establishment of a differentiated phenotype in BC3H1 mouse myoblasts. Transfection with the valine-12 allele of the human Harvey ras gene, under the control of its own promoter, was sufficient to prevent the induction of both muscle creatine kinase activity and the nicotinic acetylcholine receptor following mitogen withdrawal but did not inhibit withdrawal from the cell cycle. The loss of creatine kinase activity resulted from a corresponding block to induction of muscle creatine kinase mRNA. Similarly, mitogen withdrawal elicited little or no a-actin mRNA in ras-transfected cells. These results suggest that an activated ras allele can inhibit myogenesis through a mechanism independent of cell proliferation and can preclude activation of genes whose up-regulation normally accompanies mitogen withdrawal.
Myogenic differentiation is obligatorily coupled to withdrawal of myoblasts from the cell cycle and is inhibited by specific polypeptide growth factors. To investigate the potential involvement of c-myc in the control of myogenesis, the BC3H1 muscle cell line was stably transfected with a simian virus 40 promoter:c-myc chimeric gene. In quiescent cells in 0.5% serum, the exogenous c-myc gene was expressed at a level more than threefold greater than the level of endogenous c-myc in undifferentiated, proliferating cells of the parental line in 20% serum. The transfected myc gene partially inhibited the expression of both muscle creatine kinase and the nicotinic acetylcholine receptor, but was not sufficient to prevent the induction of these muscle differentiation products upon mitogen withdrawal.
Cardiac myocytes irreversibly lose their proliferative capacity soon after birth, and cardiac DNA synthesis becomes uncoupled from mitotic division. Therefore, we examined cardiac muscle for developmental down regulation of inducible proto-oncogenes associated with cell proliferation. c-myc mRNA decreased continuously from day 13 of embryonic development and was dissociated from expression of the fos-related gene r-fos, which decreased precipitously between days 3 and 7 after birth.
New evidence is described on one way crossing barriers Une nouvelle evidence est dkcrite sur les barribres B sens between Aigeiros and Tacamahaca species, gained in experimental unique lors des croisements entre les es@cesAigeros et Tacamafull-sib crosses. The technique of crosses and embryo rescue are haca, obtenues chez des descendants directs expkrimentaux described. In some crosses of questionable result, the embryo resobtenus par croisement. Les techniques de croisement et de cue was successful. The possible genetic mechanisms underlyricup6ration de I'embryon sont d&tes dans cet expos6 Pour cering the crossing barriers are discussed.tains croisements dont les resultats sont discutables, la rCcupiration de I'embryon a CtC faite avec succbs. Les mCcanismes gCn6-
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