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Temporal Ordering of Dynamic Expression Data from Detailed Spatial Expression Maps
Published on: February 9, 2017
A molecular timer couples organism-wide temporal identity to developmental checkpoints
Peipei Wu1, Jing Wang1, Brett Pryor2
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.
Summary
Scientists discovered a molecular timer in C. elegans that synchronizes development across tissues. This timer, involving MYRF-1 and LIN-42, ensures proper cell-fate transitions and organismal growth.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Coordinated development relies on precise temporal ordering of growth and cell-fate transitions.
- The mechanisms generating and synchronizing developmental timing across tissues are not fully understood.
- In C. elegans, microRNAs like lin-4 and let-7 drive stage-specific cell-fate changes through pulsatile transcription, but the rhythm generation is unknown.
Purpose of the Study:
- To identify the molecular mechanism responsible for generating and synchronizing developmental timing rhythms across somatic tissues in C. elegans.
- To elucidate the roles of MYRF-1 and LIN-42 in controlling microRNA transcription and developmental progression.
Main Methods:
- Identification and characterization of a transcription factor (MYRF-1) and a repressor (LIN-42) forming a developmental timer.
- Analysis of MYRF-1 binding to regulatory elements of heterochronic microRNA genes.
- Investigation of LIN-42's interaction with MYRF-1 and its effect on transcriptional activity.
- Assessment of MYRF-1's role in developmental checkpoints and ecdysis.
Main Results:
- A novel developmental timer composed of MYRF-1 and LIN-42 was identified, operating synchronously across all somatic tissues.
- MYRF-1 drives stage-specific transcriptional pulses of microRNAs by binding regulatory elements and activates lin-42 expression.
- LIN-42 directly binds MYRF-1, limiting its nuclear presence and transcriptional activity, thus controlling pulse duration and amplitude.
- MYRF-1 activity is crucial for a developmental checkpoint regulating growth and successful ecdysis.
Conclusions:
- A reciprocal transcriptional-translational feedback loop involving MYRF-1 and LIN-42 generates organism-wide developmental timing information.
- This molecular timer couples tissue-specific differentiation with coordinated organismal growth.
- The findings reveal a fundamental mechanism for synchronizing developmental progression in multicellular organisms.
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