Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis.

Journal Article (Journal Article)

Bone morphogenetic proteins (Bmps) are members of the transforming growth factor beta (TGFbeta) superfamily that play critical roles during mouse embryogenesis. Signaling by Bmp receptors is mediated mainly by Smad proteins. In this study, we show that a targeted null mutation of Ecsit, encoding a signaling intermediate of the Toll pathway, leads to reduced cell proliferation, altered epiblast patterning, impairment of mesoderm formation, and embryonic lethality at embryonic day 7.5 (E7.5), phenotypes that mimic the Bmp receptor type1a (Bmpr1a) null mutant. In addition, specific Bmp target gene expression is abolished in the absence of Ecsit. Biochemical analysis demonstrates that Ecsit associates constitutively with Smad4 and associates with Smad1 in a Bmp-inducible manner. Together with Smad1 and Smad4, Ecsit binds to the promoter of specific Bmp target genes. Finally, knock-down of Ecsit with Ecsit-specific short hairpin RNA inhibits both Bmp and Toll signaling. Therefore, these results show that Ecsit functions as an essential component in two important signal transduction pathways and establishes a novel role for Ecsit as a cofactor for Smad proteins in the Bmp signaling pathway.

Full Text

Duke Authors

Cited Authors

  • Xiao, C; Shim, J-H; Klüppel, M; Zhang, SS-M; Dong, C; Flavell, RA; Fu, X-Y; Wrana, JL; Hogan, BLM; Ghosh, S

Published Date

  • December 1, 2003

Published In

Volume / Issue

  • 17 / 23

Start / End Page

  • 2933 - 2949

PubMed ID

  • 14633973

Pubmed Central ID

  • PMC289152

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.1145603


  • eng

Conference Location

  • United States