For an animal to develop normally, cells must not only become the right types, they must do so at the right time. In the worm C. elegans, the protein LIN28 has long been known as an important regulator of this timing: it keeps cells in a flexible state and delays their shift toward adult-like forms. In humans and other mammals, related LIN28 proteins have been associated with the timing of puberty.

Because LIN28 binds many RNAs, scientists have viewed it as a regulator of large networks of genes. But a new study by researchers in the Grosshans lab suggests that its role is much more focused, at least in worms. The team found that, although LIN28 attaches to many RNA molecules, only two seem to be essential for its role in development. One of them is a conserved regulator that helps cells move toward more mature states.

When the researchers removed these two molecules in animals that also lacked LIN28, the developmental changes normally caused by LIN28 loss disappeared. But when they increased the levels of both molecules in animals with reduced LIN28 function, the worms began to resemble animals missing LIN28. In those animals, vulval development began too early, leading to a visible protruding vulva.

Animals lacking LIN28 also skipped part of the normal larval program, yet some larval stages lasted longer, suggesting that LIN28 helps coordinate both developmental identity and the pace of development.

The study offers a simpler view of how biological timing can be controlled through a small set of molecules, says senior author Helge Grosshans. The findings, he adds, also raise a question for future work: “How often do broad molecular interactions boil down to a few targets that carry most of the biological effect?”