Cold Spring Harbor Laboratory researchers report that a feedback circuit involving the proteins MYRF-1 and LIN-42 times organism-wide bursts of gene activity that help drive the roundworm C. elegans through its larval stages.
Researchers at Cold Spring Harbor Laboratory say they have identified what appears to be a central developmental timing mechanism in the tiny roundworm Caenorhabditis elegans, helping explain how the animal progresses through a precise sequence of growth stages. According to the team, two proteins—MYRF-1 and LIN-42—form a feedback circuit that controls the timing and duration of repeated pulses of gene expression that occur as the worm develops. In their account, those pulses occur in an orderly sequence and correspond to the animal’s four larval stages. > “It’s like a ratchet. It turns genes on and off multiple times during development, but ultimately, it’s only going in one direction,” professor Christopher M. Hammell said in a Cold Spring Harbor Laboratory statement. The researchers reported that disrupting MYRF-1 halts developmental progression, consistent with the idea that the circuit is required for the staged program to run. They also said their work represents the first example of a “non-repeating” biological clock of this kind—one designed to coordinate a finite, one-way series of developmental events rather than an endlessly cycling rhythm. The study was published in Proceedings of the National Academy of Sciences. The researchers said they combined molecular biology experiments with sequencing approaches and used the protein-structure prediction system AlphaFold to help characterize how components of the circuit interact. While the work was done in a worm, the authors argue that identifying a mechanism that links temporal “identity” cues to developmental checkpoints could help researchers think about how timing systems fail in other organisms—an angle they say may be relevant to understanding some growth- and development-related disorders.
