MODULATION OF MYOGENIC DETERMINATION FACTOR-I EXPRESSION BY CELL-CELLCONTACT

Myogenic determination factor 1 (MyoD1) expression is modulated by a v ariety of agents including growth factors and activated cellular proto -oncogenes. However, little is known about the effect of cell-cell con tact, which increases as myoblasts terminally differentiate, on the co ntrol of MyoD1 expression. Steady-state levels of MyoD1 transcripts de cline over a 6-12 hour time period when myoblasts plated at a single c ell density are incubated in media supplemented with 0.2% serum; by 48 hours MyoD1 mRNA levels have returned to the initial basal level. The decline in MyoD1 transcripts is diminished, but not prevented in myob lasts which maintain cell-cell contacts (at least 50% of cells with tw o or more sites of contact). MyoD1 transcript levels do not change if single cell cultures are maintained in 10% serum or are cocultured wit h fibroblasts. Analysis of conditioned media revealed that myoblasts p lated at the single cell density or at a density which allowed multipl e sites of cell-cell contact are not producing an activity(s) responsi ble for modulating MyoD1 mRNA levels. The changes in MyoD1 expression are mediated at the transcriptional level. Thus changes in the degree of cell-cell contact in cultures of myogenically determined cell lines effect changes in MyoD1 gene expression. Consequently when the influe nce of cytokines or other pharmacological agents on commitment to term inal myogenic differentiation is examined, the degree of cell-cell con tact within the culture system may affect the response elicited. (C) 1 993 Wiley-Liss, Inc.