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A Notch feeling of somite segmentation and beyond
Padmashree C G Rida1, Nguyet Le Minh, Yun Jin Jiang
1Laboratory of Developmental Signalling and Patterning, Institute of Molecular and Cell Biology, National University of Singapore, Singapore 117604, Singapore.
Developmental Biology
|December 31, 2003
Summary
Embryonic segmentation relies on a molecular clock mechanism involving Notch signaling for somitogenesis. This oscillator, driven by cyclical gene expression and feedback, ensures proper formation of body segments in vertebrates.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Vertebrate segmentation occurs during embryonic development, forming somites that yield vertebrae, ribs, muscle, and dermis.
- The
- clock and wavefront
- model and Notch-Delta signaling are key concepts in understanding somitogenesis.
Purpose of the Study:
- To elucidate the fundamental mechanism underlying the segmentation clock in vertebrate embryonic development.
- To highlight the critical role of Notch signaling in somitogenesis.
- To compare the segmentation clock with the circadian clock.
Main Methods:
- Review of genetic evidence from model organisms (mouse, chick, Xenopus, zebrafish).
- Analysis of molecular pathways including Notch-Delta signaling, Hairy/E(spl) homologues, Fgf8, and Wnt3a.
- Discussion of theoretical models and mathematical modeling approaches.
Main Results:
- A segmentation clock mechanism involving cyclical transcriptional activation and delayed negative feedback is emerging.
- Notch signaling is indispensable for somitogenesis, regulating the segmentation clock.
- Ubiquitin-dependent protein degradation and other posttranslational regulations are necessary.
- Fgf8 and Wnt3a gradients influence somite boundary positioning and coordination of development.
Conclusions:
- The segmentation clock is a biochemical oscillator primarily exploiting the Notch pathway for signal generation and synchronization.
- The segmentation clock shares similarities with the circadian clock in its feedback mechanism but utilizes a distinct pathway.
- Further research directions and mathematical modeling are crucial for a comprehensive understanding.