MyoD: A Master Regulatory Gene for Myogenesis 
seem to provide information about cell type. Id 
(inhibitor of differentiation) offers a pathway for 
negative control. And E2A may perform an effec- 
tor or integration function yet to be defined fully. 
These types of inputs then seem to be integrated 
by HLH interactions betvv^een pairs of individual 
monomers, and the result seems to be a specific 
binding capacity. For protein complexes contain- 
ing Id, the choice is probably on-or-off; for com- 
plexes of E2A or MyoD homodimers or hetero- 
dimers, the result can be altered DNA-binding 
specificity. Although it is clear that interactions 
between HLH proteins are very precise and spe- 
cific, the rules are not yet known. 
MyoD Is Controlled by and Can Control the 
State of Cell Growth 
A variety of agents specifically inhibit myo- 
genic differentiation. The list includes genes 
such as ras, fos, jun, fps, erbA, myc, and El A; 
chemical agents such as butyrate and phorbol es- 
ters; and growth factors such as FGF and FGF|8. 
Most of these reagents can inactivate the ex- 
pressed MyoD protein, and several, such as ras 
and fos, also inhibit MyoD transcription. The spe- 
cific pathway by which each of these oncogenes, 
anti-oncogenes, and growth factors inhibits myo- 
genesis provides a clue to how MyoD might inte- 
grate information coming from many aspects of 
cellular function. 
Factors that influence growth regulate MyoD, 
but MyoD itself can also inhibit cell growth. Ex- 
periments with MyoD mutants show that the HLH 
domain is required for growth arrest. 
Activation of MyoD During Development 
Recently, the MyoD gene has been cloned from 
Caenorhabditis elegans, and an antibody to the 
protein, produced. The antibody first stains cells 
at the 100-cell stage. These are lineage founder 
cells fated to give rise to body wall muscle de- 
scendants some three to four generations later. 
Less than 3 kb of the upstream control region of 
MyoD is needed for body wall muscle-specific 
expression, as revealed by fusing these sequences 
to a /3-galactosidase expression reporter. Results 
suggest that the capacity for transcription of 
MyoD in a myogenic lineage may precede the 
actual cell type-specific expression of the pro- 
tein, and this capacity segregates into specific 
blastomeres as early as the 28-cell stage. Presum- 
ably, subsequent cell-cell interactions determine 
which descendants will give rise to nerve and 
skin and turn off MyoD transcription and which 
will maintain MyoD expression and give rise to 
skeletal muscle cells. 
Conclusion 
The flow of cell type-specific information for 
myogenesis from the egg to the final muscle cell 
goes through a nodal point, defined by functions 
supplied by the MyoD family of myogenic regula- 
tory proteins. It is possible that the achaete-scute 
complex of genes also acts as a nodal point, but 
for neurogenesis. An alternative organization 
could have also been imagined: combinations of 
less tissue-restricted genes could have encoded 
the MyoD or achaete-scute functions. The nodal 
point need not have been an optimal solution, 
but simply one that worked at some crucial time 
during evolution. Whether other cell lineages 
employ this strategy, and whether there is a pro- 
found insight provided by its use (such as the 
potential to make cell types mutually exclusive), 
await further analysis. 
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