The MyoD Gene Family: A Nodal Point During Specification 
of Muscle Cell Lineage 
effect due to an inhibition of the autoactivation 
function of MyoD protein or a more direct inhibi- 
tion of MyoD transcription remains to be deter- 
mined. Rhabdomyosarcoma cells (derived from 
tumors of patients who harbor a genetic predis- 
position to myogenic tumors) differentiate 
poorly but express MyoD, suggesting that loss of 
anti-oncogene activity at the rhabdomyosarcoma 
locus can also impinge on MyoD action. The spe- 
cific pathway by which each of these oncogenes, 
anti-oncogenes, and growth factors inhibits myo- 
genesis provides a potential clue to how MyoD 
might integrate information coming from many 
aspects of cellular function. 
Recently, in collaboration with the laboratory of 
Inder Verma, we found that the leucine zipper re- 
gion of the jun oncogene actually binds to the he- 
lix-loop-helix region of MyoD, both in vivo and in 
vitro. Similarly, assays for a recognition factor for 
MyoD activation show that such a factor, which is 
missing in rhabdomyosarcoma cell lines, can be 
provided in trans by fusion with 1 OTVi cells. Possi- 
bly failure to activate myogenesis leads to increased 
proliferation and then secondary effects that give 
rise to rhabdomyosarcomas. 
Activation of MyoD During Development 
We are studying developmental activation of 
MyoD in mice, worms, and frogs. In both mice 
and worms, deletional analysis has identified 
regulatory sequences upstream of the MyoD 
gene that are important for correct developmen- 
tal activation of MyoD. Current efforts focus on 
identifying trans-acting elements that integrate 
with these sequences. In worms, several mater- 
nal-effect mutants have been isolated by Jim 
Priess and his colleagues. These mutant em- 
bryos produce excess muscle from the wrong 
lineage. It is possible that these mutants define 
elements involved in the segregation of myo- 
genic potential to specific cells during early 
cleavage stages. In apparent contrast to worms, 
frogs seem to activate MyoD in all cells of the 
blastoderm; however, expression is stabilized 
only in those presumptive mesodermal cells 
that become induced by vegetal inducing fac- 
tors such as activin. Frogs also contain maternal 
MyoD mRNA, which, however, seems not to be 
crucial for subsequent myogenesis, as its de- 
struction with anti-sense DNA results in normal 
muscle gene activation. 
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