Extraembryonic Signals under the Control of MGA, Max, and Smad4 Are Required for Dorsoventral Patterning

• Published in: Developmental cell 2014-02, Vol.28 (3), p.322-334
• Main Authors: Sun, Yuhua, Tseng, Wei-Chia, Fan, Xiang, Ball, Rebecca, Dougan, Scott T.
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Blotting, Western; Body Patterning; Bone Morphogenetic Protein 2 - genetics; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Gene Expression Regulation, Developmental; Immunoenzyme Techniques; Immunoprecipitation; Real-Time Polymerase Chain Reaction; Regulatory Elements, Transcriptional; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal Transduction; Smad4 Protein - genetics; Smad4 Protein - metabolism; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2014.01.003

In vertebrates, extraembryonic tissues can act as signaling centers that impose a reproducible pattern of cell types upon the embryo. Here, we show that the zebrafish yolk syncytial layer (YSL) secretes a ventralizing signal during gastrulation. This activity is mediated by Bmp2b/Swirl (Swr) expressed under the control of Max’s giant associated protein (MGA) and its binding partners, Max and Smad4. MGA coimmunoprecipitates with both Max and Smad4 in embryo extracts, and the three proteins form a complex in vitro. Furthermore, all three proteins bind to a DNA fragment upstream of the bmp2b transcription start site. Targeted depletion of MGA, its binding partners, or Bmp2b/Swr from the YSL reduces BMP signaling throughout the embryo, resulting in a mildly dorsalized phenotype. We conclude that MGA, Max, and Smad4 act in the extraembryonic YSL to initiate a positive feedback loop of Bmp signaling within the embryo. [Display omitted] •MGA forms a complex with both Max and Smad4 in embryos•The MH2 domain of Smad4 binds to MGA, and the MH1 domain binds Max•The MGA/Max/Smad4 complex binds a cis-regulatory element at the bmp2b/swr locus•MGA/Max/Smad4 act in the yolk syncytial layer to reinforce ventralization via BMP Sun et al. demonstrate that extraembryonic BMP signals in zebrafish are under the control of a protein complex containing Max’s giant associated protein (MGA), Max, and Smad4. Previously, MGA was known only as an antagonist of Myc function. These results provide a molecular link between cell proliferation and embryonic patterning.