黑料吃瓜资源

Imagine a train parked at the station. Passengers climb aboard and find their seats. Conductors move up and down the aisles, checking tickets. But there鈥檚 a problem鈥攖he engineer鈥檚 watch is broken. As a result, the doors never close, the whistle never sounds, and the train never starts. Something similar occurs in cells when developmental timing is disrupted. Rather than making people late for work, it can mean the difference between maturing into a healthy adult and never growing up at all.

In the worm C. elegans, 黑料吃瓜资源 (CSHL) Professor Christopher Hammell and his team previously discovered how pulses of gene expression drive development. However, the mechanism behind their precise timing remained a mystery. Now, the team has found that a feedback circuit composed of two previously known proteins, MYRF-1 and LIN-42, acts as the worm genome鈥檚 master developmental clock, scheduling the start and duration of each pulse. This is the first non-repeating biological clock of its kind ever found.

鈥淭his is the central clock for all cells in the worm,鈥� Hammell explains. 鈥淚t鈥檚 responsible for coordinating a finite series of sequential pulses of gene expression that must occur only once, and in order, for proper developmental progression. It鈥檚 like a ratchet. It turns genes on and off multiple times during development, but ultimately, it鈥檚 only going in one direction.鈥�

Using a combination of classical molecular experiments, DNA and protein sequencing, and the AI tool AlphaFold, the team zeroed in on the key roles MYRF-1 plays in C. elegans development. Remarkably, they found that the protein acts as the starting gun and is essential for the checkpoint at the end of each developmental stage. Once a pulse of gene expression has started, MYRF-1 also activates LIN-42, which controls the strength and duration of each pulse. When the team blocked MYRF-1, it disrupted the entire developmental cycle.

鈥淲e鈥檝e never seen anything like this before,鈥� Hammell says. 鈥淢YRF-1 is part of this master regulatory clock for all cells, but it鈥檚 also acting as a key maker and the master key for each stage of growth. Without the right key for each stage, development hits a wall and can鈥檛 progress.鈥�

The team, which also includes CSHL Director of Research Leemor Joshua-Tor, is now investigating how LIN-42 and MYRF-1 physically interact and how each of these cellular clocks communicates with others during development. Understanding how these clocks operate in sync opens the door for future studies on cellular growth, progression, and differentiation.

鈥淭丑别 MYRF-1/LIN-42 circuit runs in all cells,鈥� Hammell says. 鈥淎nd every one of these independent cellular clocks appears to be in sync when you watch normal development. But are they communicating with each other? We鈥檝e never thought deeply about that question before.鈥�

Addressing it could one day provide insight into genetic diseases and developmental disorders, helping 鈥減ull the train out of the station鈥� for countless lives needlessly cut short.

Written by: Nick Wurm, Communications Specialist | [email protected] | 516-367-5940

Funding

National Institutes听of Health, National Science Foundation, National Human Genome Research Institute, National Institute听of听General听Medical听Sciences

Citation

Wu, P.,听et al., 鈥�A molecular timer听couples听organism-wide temporal identity to developmental checkpoints鈥�,听PNAS,听May 6, 2026. DOI:听

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