Wu, Peipei, Wang, Jing, Pryor, Brett, Valentino, Isabella, Ritter, David F, Loel, Kaiser, Yarychkivska, Olya, Shaham, Shai, Kinney, Justin, Ercan, Sevinc, Joshua-Tor, Leemor, Hammell, Christopher M (May 2026) A molecular timer couples organism-wide temporal identity to developmental checkpoints. Proceedings of the National Academy of Sciences of the United States of America, 123 (19). e2606846123. ISSN 0027-8424 (Public Dataset)
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Abstract
Coordinated development requires that growth and cell-fate transitions occur in a defined temporal order across tissues, yet how multicellular organisms generate and synchronize developmental timing information remains unclear. In Caenorhabditis elegans, stage-specific cell-fate transitions are driven by pulsatile transcription of microRNAs, including lin-4 and let-7 family members, but the mechanism that produces these rhythms has been unknown. Here, we identify a developmental timer composed of the transcription factor MYRF-1 and the PERIOD-like repressor LIN-42 that operates synchronously across all somatic tissues. MYRF-1 binds conserved regulatory elements upstream of heterochronic microRNA genes and drives once-per-stage transcriptional pulses that are phase-locked across tissues, while simultaneously activating lin-42 expression. Newly synthesized LIN-42 directly associates with MYRF-1, limiting its nuclear residence and transcriptional activity and thereby constraining the amplitude and duration of each pulse. Beyond regulating stage-specific gene expression, we show that MYRF-1 activity is also required to license a developmental checkpoint essential for growth and successful ecdysis. Together, these findings define a reciprocal transcriptional-translational feedback loop that generates organism-wide developmental timing information, coupling tissue-specific differentiation programs to coordinated organismal growth through a shared molecular timer.
| Item Type: | Paper |
|---|---|
| Subjects: | organism description > animal > C elegans organism description > animal organism description > animal > developmental stage |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL labs > Jackson lab CSHL labs > Joshua-Tor lab CSHL labs > Kinney lab CSHL Cancer Center Program CSHL Post Doctoral Fellows School of Biological Sciences > Publications |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 12 May 2026 |
| Date Deposited: | 11 May 2026 13:10 |
| Last Modified: | 11 May 2026 13:10 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/42195 |
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