The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program

• Published in: Nature communications 2011-07, Vol.2 (1), p.390-390, Article 390
• Main Authors: Chalamalasetty, Ravindra B., Dunty, William C., Biris, Kristin K., Ajima, Rieko, Iacovino, Michelina, Beisaw, Arica, Feigenbaum, Lionel, Chapman, Deborah L., Yoon, Jeong Kyo, Kyba, Michael, Yamaguchi, Terry P.
• Format: Article
• Language: English
• Subjects: 631/136/1455; 631/208/191/2018; 631/80/86; Animals; Basic Helix-Loop-Helix Transcription Factors - physiology; beta Catenin - metabolism; Biological Clocks - physiology; Body Patterning - physiology; Cell Differentiation; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Embryonic Stem Cells; Gene Expression Profiling; Humanities and Social Sciences; In Situ Hybridization; Mice; Mice, Transgenic; multidisciplinary; Receptors, Notch - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Science; Science (multidisciplinary); Signal Transduction - physiology; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt3 Protein; Wnt3A Protein
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1381

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. During development, Wnt-mediated Notch signalling controls the generation of somites from the presomitic mesoderm, but the precise signalling mechanism is unknown. Here, the transcription factor Mesogenin 1 is shown to be a direct target of Wnt3a and regulates the transcription of a Notch signalling program.