The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite.
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.
Morimoto
Mitsuru
M
Division of Mammalian Development, National Institute of Genetics, Yata 1111, Mishima 411-8540, Japan.
Sasaki
Nobuo
N
Oginuma
Masayuki
M
Kiso
Makoto
M
Igarashi
Katsuhide
K
Aizaki
Ken-ichi
K
Kanno
Jun
J
Saga
Yumiko
Y
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D019521:Body Patterning; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D019170:Somites / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D016695:Glycosyltransferases; D012097:Repressor Proteins; C107407:Mesp2 protein, mouse; C520509:Ripply2 protein, mouse; C498392:Lfng protein, mouse