title: The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
abstract: Segmentation is an organizing principle of body plans. The segmentation clock, a molecular oscillator best illustrated by the cyclic expression of Notch signalling genes, controls the periodic cleavage of somites from unsegmented presomitic mesoderm during vertebrate segmentation. Wnt3a controls the spatiotemporal expression of cyclic Notch genes; however, the underlying mechanisms remain obscure. Here we show by transcriptional profiling of Wnt3a (-/-) embryos that the bHLH transcription factor, Mesogenin1 (Msgn1), is a direct target gene of Wnt3a. To identify Msgn1 targets, we conducted genome-wide studies of Msgn1 activity in embryonic stem cells. We show that Msgn1 is a major transcriptional activator of a Notch signalling program and synergizes with Notch to trigger clock gene expression. Msgn1 also indirectly regulates cyclic genes in the Fgf and Wnt pathways. Thus, Msgn1 is a central component of a transcriptional cascade that translates a spatial Wnt3a gradient into a temporal pattern of clock gene expression.
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, Maryland 21702, USA.
authors.forename: Ravindra B
authors.initials: RB
authors.lastname: Chalamalasetty
authors.forename: William C
authors.initials: WC
authors.lastname: Dunty
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Biris
authors.forename: Rieko
authors.initials: R
authors.lastname: Ajima
authors.forename: Michelina
authors.initials: M
authors.lastname: Iacovino
authors.forename: Arica
authors.initials: A
authors.lastname: Beisaw
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Chapman
authors.forename: Jeong Kyo
authors.initials: JK
authors.lastname: Yoon
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D053595:Embryonic Stem Cells; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; C410883:Msgn1 protein, mouse; C555511:Wnt3a protein, mouse