Imagine a train stopping at a station. Passengers board, the conductor checks their tickets, and everything appears to be ready. However, if the engineer’s clock stops, the train will never depart. The door remains open, the whistle never sounds, and the journey never begins.
Similar problems can occur within living cells. If the timing systems that control development do not function, the organism may not be able to go through the stages necessary to reach adulthood.
Researchers at Cold Spring Harbor Laboratory (CSHL) have identified what appears to be the tiny worm’s master developmental clock. nematode. The discovery reveals how cells maintain growth and development on schedule by orchestrating a series of carefully timed bursts of gene activity.
Scientists identify master developmental clock
A few years ago, CSHL Professor Christopher Hummel and his colleagues nematode Driven by pulses of gene expression. These bursts of gene activity occur in sequence and help guide each stage of an organism’s growth.
What remained unclear was how these pulses were timed so precisely.
The research team now discovers that two proteins, MYRF-1 and LIN-42, form a feedback circuit that acts as a central developmental clock in the C. elegans genome. Together, these determine when each pulse of gene expression begins and how long it lasts. Researchers say this is the first example of a non-repetitive biological clock of its kind.
“This is the central clock in every cell of the worm,” Hamel explains. “It’s responsible for coordinating a finite series of pulses of gene expression that must occur only once for development to proceed properly. It’s like a ratchet: genes are switched on and off many times during development, but ultimately they only go in one direction.”
How MYRF-1 and LIN-42 control proliferation
To uncover the clock mechanism, the researchers combined traditional molecular biology experiments with DNA sequencing, protein sequencing, and the artificial intelligence tool AlphaFold.
Their findings revealed that MYRF-1 plays several important roles during development. This protein serves as a trigger to initiate each developmental stage and is also required at checkpoints that mark its completion.
When a burst of gene activity begins, MYRF-1 activates LIN-42. LIN-42 helps regulate the strength and duration of the genetic pulse. Combining the two proteins ensures that development proceeds in the right order and at the right pace.
When researchers blocked MYRF-1, the entire developmental program collapsed.
“We’ve never seen anything like this before,” Hamel said. “MYRF-1 is part of the master regulatory clock in all cells, but it also acts as a key maker and master key for each stage of growth. Without the right key for each stage, development will hit a wall and no progress can be made.”
Explore how your phone’s clock stays in sync
The research team also includes Leemore Joshua-Toll, director of research at CSHL. Their next goal is to better understand how MYRF-1 and LIN-42 physically interact and how these developmental clocks function across different cells.
One of the most interesting questions is whether individual watches will communicate with each other during development.
“The MYRF-1/LIN-42 circuit works in every cell,” says Hammell. “And when you look at normal development, all these independent mobile clocks seem to be in sync. But are they communicating with each other? We’ve never really thought about that question before.”
Potential impact on developmental disorders
Understanding how developmental clocks function and remain synchronized can provide important insights into cell growth, differentiation, and tissue and organ progression.
In the future, this research could help scientists better understand developmental disorders and certain genetic diseases. By revealing how the body’s timing system keeps growth moving forward, the findings could ultimately point to new ways to deal with situations in which normal development is disrupted.
Like a train that finally receives the signal to leave the station, the newly discovered MYRF-1/LIN-42 clock appears to help ensure development moves forward one step at a time.
