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The vertebrate segmentation clock
François Giudicelli1, Julian Lewis
1Vertebrate Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. francois.giudicelli@cancer.org.uk
Current Opinion in Genetics & Development
|July 21, 2004
Summary
Somite segmentation in vertebrate embryos relies on a molecular clock within the presomitic mesoderm. This clock
Area of Science:
- Developmental biology
- Molecular genetics
- Systems biology
Background:
- Somite segmentation is a fundamental process in vertebrate embryonic development.
- A molecular clock mechanism, primarily involving the Notch pathway, controls somite segmentation.
- The Wnt pathway gene Axin2 is a notable exception to Notch pathway involvement.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the somite segmentation clock.
- To explore the role of negative feedback loops in generating oscillations.
- To analyze the contribution of transcriptional and translational delays to the oscillation period.
Main Methods:
- Analysis of Notch pathway genes and Wnt pathway gene Axin2.
- Experimental investigation of negative feedback loops.
- Mathematical modeling of the transcriptional oscillator.
Main Results:
- Identified direct autoinhibition of hairy/E(spl) family genes (Hes7, her1, her7) as a key oscillatory mechanism.
- Mathematical modeling supported this simple feedback loop.
- Demonstrated that transcriptional and translational delays primarily determine the oscillation period.
Conclusions:
- Direct autoinhibition of Hes7/her1/her7 is a plausible mechanism for the somite segmentation clock.
- Transcriptional and translational delays are critical determinants of the clock's period.
- This provides insights into the regulation of embryonic patterning.