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The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity
Mitsuru Morimoto1, Yu Takahashi, Maho Endo
1Division of Mammalian Development, National Institute of Genetics, Mishima, Japan.
Nature
|May 20, 2005
Summary
Vertebrate segmentation relies on somites. This study reveals Notch activity oscillates in the posterior presomitic mesoderm and is arrested in the anterior, forming somite boundaries via Mesp2 and Lfng.
Area of Science:
- Developmental biology
- Embryogenesis
- Molecular biology
Background:
- Vertebrate segmentation involves somite formation.
- The 'clock and wavefront' model explains somite periodicity via Notch signaling oscillations.
- Direct evidence for Notch oscillation and its translation into segmental patterns is lacking.
Purpose of the Study:
- To visualize endogenous Notch1 activity dynamics during mouse embryogenesis.
- To elucidate the mechanism of somite boundary formation.
- To investigate the role of Mesp2 and Lfng in translating Notch oscillations.
Main Methods:
- In vivo visualization of endogenous Notch1 activity in mice.
- Genetic manipulation of Notch signaling components.
- Biochemical analysis of gene interactions.
Main Results:
- Notch1 activity oscillates in the posterior presomitic mesoderm (PSM).
- Notch1 activity is arrested in the anterior PSM, forming the wavefront.
- Somite boundaries form at the interface of activated and repressed Notch1 domains.
- Mesp2 suppresses Notch activity by inducing Lfng, creating this interface.
Conclusions:
- The study provides direct evidence for oscillating and arrested Notch activity during somite formation.
- Mesp2-induced Lfng mediates the translation of temporal Notch oscillations into spatial somite boundaries.
- This mechanism clarifies how the 'clock and wavefront' model generates vertebrate metameric structures.
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