RRC ID 1727
Author Morimoto M, Takahashi Y, Endo M, Saga Y.
Title The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity.
Journal Nature
Abstract The serially segmented (metameric) structures of vertebrates are based on somites that are periodically formed during embryogenesis. A 'clock and wavefront' model has been proposed to explain the underlying mechanism of somite formation, in which the periodicity is generated by oscillation of Notch components (the clock) in the posterior pre-somitic mesoderm (PSM). This temporal periodicity is then translated into the segmental units in the 'wavefront'. The wavefront is thought to exist in the anterior PSM and progress backwards at a constant rate; however, there has been no direct evidence as to whether the levels of Notch activity really oscillate and how such oscillation is translated into a segmental pattern in the anterior PSM. Here, we have visualized endogenous levels of Notch1 activity in mice, showing that it oscillates in the posterior PSM but is arrested in the anterior PSM. Somite boundaries formed at the interface between Notch1-activated and -repressed domains. Genetic and biochemical studies indicate that this interface is generated by suppression of Notch activity by mesoderm posterior 2 (Mesp2) through induction of the lunatic fringe gene (Lfng). We propose that the oscillation of Notch activity is arrested and translated in the wavefront by Mesp2.
Volume 435(7040)
Pages 354-9
Published 2005-5-19
DOI 10.1038/nature03591
PII nature03591
PMID 15902259
MeSH Animals Base Sequence Basic Helix-Loop-Helix Transcription Factors Biological Clocks / physiology Embryo, Mammalian Embryonic Development / genetics Embryonic Development / physiology* Enhancer Elements, Genetic / genetics Gene Deletion Gene Expression Regulation, Developmental* Glycosyltransferases / deficiency Glycosyltransferases / genetics Glycosyltransferases / metabolism Mice Models, Biological Periodicity RNA, Messenger / genetics RNA, Messenger / metabolism Receptor, Notch1 Receptors, Cell Surface / metabolism* Somites / metabolism Transcription Factors / genetics Transcription Factors / metabolism*
IF 43.07
Times Cited 168