Scientists at the Cold Spring Harbor Laboratory have discovered there is a rhythm to the development of the C elegans worm

There’s a rhythm to developing life. Growing from a tiny cell cluster into an adult organism takes precise timing and control.

The right genes must turn on at the right time, for the right duration, and in the correct order.

Losing the rhythm can lead to diseases like cancer. So, what keeps every gene on beat?

Cold Spring Harbor Laboratory (CSHL) Professor Christopher Hammell has found that in the worm C elegans, this genetic orchestra has no single conductor.

Instead, a quartet of molecules works in concert to time each developmental stage.

Hammell says this process shares some similarities with the circadian clocks that control human behaviour.

Understanding how the worm’s clock is regulated could help explain how time affects development in other animals.

Hammell explained: “This clock we’ve discovered sets the cadence of development.

It’s a co-ordinator of the orchestra.

“It controls when the trombone goes, how loud it gets, and how long the note lasts.”



C elegans’ development


Each stage of C elegans’ development begins with two proteins, NHR-85 and NHR-23.

They work together to spark a pulse of gene expression, switching on the microRNA lin-4, which controls stem cell development patterns.

The pulse’s timing, strength, and duration depend on the short stretch when NHR-85 and NHR-23 interact, and another protein, LIN-42, which ends each developmental period by shutting off NHR-85.

Hammell said: “Mess up the orchestra – it’ll still make sound, but the way the music changes lets us know proper timing is critical for development.”

Hammell teamed with Wolfgang Keil from the Curie Institute in Paris to observe this gene expression cycle in action. 

C elegans takes about 50 hours to reach adulthood.

During that time, it’s always on the move, like a restless teenager.

The team developed a new imaging technique to hold the tiny worm in place long enough to take pictures and video.

This let them measure each developmental beat as it occurred.

Hammell said: “We could see every time genes turned on from birth to adulthood.

“This kind of imaging had never been done in animals, only in single cells.”

Hammell is now working with CSHL Professor & HHMI Investigator Leemor Joshua-Tor to image how clock proteins interact over time.

Hammel said: “We want to work out, with even more precision, how this clock operates.

“Humans can do things like write music or perform calculus, not because we have a calculus or music gene, but because our developmental clocks enable our brain to develop longer into a more complex organ.”

In other words, when it comes to development, time is truly of the essence.

Image: To observe development in the C. elegans worm, seen here, Professor Christopher Hammell’s team at the CSHL Cancer Center expanded upon an imaging technique originally developed for use in single cells. This allowed them to witness, for the first time, active gene expression taking place inside an animal. Credit: Christopher Hammell/Cold Spring Harbor Laboratory.

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