title: The negative regulation of Mesp2 by mouse Ripply2 is required to establish the rostro-caudal patterning within a somite.
abstract: 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.
authors.affiliation: Division of Mammalian Development, National Institute of Genetics, Yata 1111, Mishima 411-8540, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Morimoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Oginuma
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Aizaki
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: 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*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016695:Glycosyltransferases; D012097:Repressor Proteins; C107407:Mesp2 protein, mouse; C520509:Ripply2 protein, mouse; C498392:Lfng protein, mouse