Ready, set, wait

Stem cell differentiation is all about cautious preparation, say Deborah Lang, Jonathan Epstein (University of Pennsylvania, Philadelphia, PA), and colleagues. They find that a transcription factor called Pax3 sends conflicting messages: it gets stem cells ready for the differentiated state, by building up proteins used in the differentiation program, but inhibits the action of those differentiation proteins and thus holds the cells back. Only a separate signal can relieve this repression by Pax3 and unleash the full differentiation program.

“The general concept that there are classes of transcription factors that yield paradoxical results—both activating and inactivating pathways—has been around,” says Epstein. “What's an addition here is a molecular mechanism.”

Epstein's group came across the phenomenon while studying neural crest cells. Pax3 was required in mice for the eventual induction of melanocyte differentiation...