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

Ravindra B. Chalamalasetty, William C. Dunty, Kristin K. Biris, Rieko Ajima, Michelina Iacovino, Arica Beisaw, Lionel Feigenbaum, Deborah L. Chapman, Jeong Kyo Yoon, Michael Kyba and Terry P. Yamaguchi ()
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Ravindra B. Chalamalasetty: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH
William C. Dunty: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH
Kristin K. Biris: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH
Rieko Ajima: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH
Michelina Iacovino: University of Minnesota
Arica Beisaw: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH
Lionel Feigenbaum: Laboratory Animal Sciences Program, National Cancer Institute-Frederick
Deborah L. Chapman: University of Pittsburgh
Jeong Kyo Yoon: Center for Molecular Medicine, Maine Medical Center Research Institute
Michael Kyba: University of Minnesota
Terry P. Yamaguchi: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, NIH

Nature Communications, 2011, vol. 2, issue 1, 1-12

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1381

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