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There鈥檚 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?

Laboratory(麻豆传媒社区) 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 behavior. Understanding how the worm鈥檚 clock is regulated could help explain how time affects development in other animals. Hammell explains:

鈥淭his clock we鈥檝e discovered sets the cadence of development. It鈥檚 a coordinator of the orchestra. It controls when the trombone goes, how loud it gets, and how long the note lasts.鈥�

Each stage of C. elegans鈥� 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鈥檚 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.

鈥淢ess up the orchestra鈥攊t’ll still make sound,鈥� Hammell says. 鈥淏ut the way the music changes lets us know proper timing is critical for development.鈥�

Hammell teamed with Wolfgang Keil from Paris鈥� Curie Institute to observe this gene expression cycle in action. C. elegans takes about 50 hours to reach adulthood. During that time, it鈥檚 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.

鈥淲e could see every time genes turned on from birth to adulthood,鈥� Hammell says. 鈥淭his kind of imaging had never been done in animals, only in single cells.鈥�

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

鈥淲e want to work out, with even more precision, how this clock operates,鈥� Hammell says. 鈥淗umans 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.鈥�

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

Written by: Nick Wurm, Communications Specialist | wurm@cshl.edu | 516-367-5940

Funding

National Institutes of Health, National Science Foundation, CNRS ATIP/Avenir program, Conseil Regional d鈥櫭巐e de France, Fondation pour la Recherche M茅dicale.

Citation

Kinney, B., et al., 鈥淎 circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans 诲别惫别濒辞辫尘别苍迟鈥�, Developmental Cell, August 28, 2023. DOI:

Core Facilites

鈥淭丑别 Microscopy Core Facility provides training, consultation, experimental design and technical assistance to investigators at Laboratoryin widefield, spinning disk laser scanning or point laser scanning confocal fluorescence microscopy, and super-resolution microscopy. In addition, the Microscopy Shared Resource provides customized state-of-the-art optical imaging and quantitative image analysis applications to support a wide range of scientific endeavors.鈥� 鈥� Director Erika Wee, Ph.D.