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First published online 14 March 2007
doi: 10.1242/dev.000836
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1 Division of Mammalian Development, National Institute of Genetics, Yata 1111,
Mishima 411-8540, Japan.
2 SOKENDAI, Yata 1111, Mishima 411-8540, Japan.
3 Cellular and Molecular Toxicology Division, National Institute of Health
Sciences, 1-18-1 Kamiyoga, Setagayaku, Tokyo 158-8501, Japan.
Author for correspondence (e-mail:
ysaga{at}lab.nig.ac.jp)
Accepted 14 February 2007
The Mesp2 transcription factor plays essential roles in segmental border formation and in the establishment of rostro-caudal patterning within a somite. A possible Mesp2 target gene, Ripply2, was identified by microarray as being downregulated in the Mesp2-null mouse. Ripply2 encodes a putative transcriptional co-repressor containing a WRPW motif. We find that Mesp2 binds to the Ripply2 gene enhancer, indicating that Ripply2 is a direct target of Mesp2. We then examined whether Ripply2 is responsible for the repression of genes under the control of Mesp2 by generating a Ripply2-knockout mouse. Unexpectedly, Ripply2-null embryos show a rostralized phenotype, in contrast to Mesp2-null mice. Gene expression studies together with genetic analyses further revealed that Ripply2 is a negative regulator of Mesp2 and that the loss of the Ripply2 gene results in the prolonged expression of Mesp2, leading to a rostralized phenotype via the suppression of Notch signaling. Our study demonstrates that a Ripply2-Mesp2 negative-feedback loop is essential for the periodic generation of the rostro-caudal polarity within a somite.
Key words: Somitogenesis, Notch signaling, Presomitic mesoderm, Segmentation
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