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

Changchun Xiao, Jae Hyuck Shim, Michael Klüppel, Samuel Shao Min Zhang, Chen Dong, Richard A. Flavell, Xin Yuan Fu, Jeffrey L. Wrana, Brigid L M Hogan, Sankar Ghosh

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Bone morphogenetic proteins (Bmps) are members of the transforming growth factor β (TGFβ) 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.

Original languageEnglish (US)
Pages (from-to)2933-2949
Number of pages17
JournalGenes and Development
Volume17
Issue number23
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Smad Proteins
Mesoderm
Embryonic Development
Germ Layers
Bone Morphogenetic Proteins
Transforming Growth Factors
Small Interfering RNA
Signal Transduction
Cell Proliferation
Phenotype
Gene Expression
Mutation
Genes

Keywords

  • BMP signaling
  • Mesoderm development
  • NF-κ B
  • Smads
  • TGF β
  • Toll-pathway

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Xiao, C., Shim, J. H., Klüppel, M., Zhang, S. S. M., Dong, C., Flavell, R. A., ... Ghosh, S. (2003). Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis. Genes and Development, 17(23), 2933-2949. https://doi.org/10.1101/gad.1145603

Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis. / Xiao, Changchun; Shim, Jae Hyuck; Klüppel, Michael; Zhang, Samuel Shao Min; Dong, Chen; Flavell, Richard A.; Fu, Xin Yuan; Wrana, Jeffrey L.; Hogan, Brigid L M; Ghosh, Sankar.

In: Genes and Development, Vol. 17, No. 23, 01.12.2003, p. 2933-2949.

Research output: Contribution to journalArticle

Xiao, C, Shim, JH, Klüppel, M, Zhang, SSM, Dong, C, Flavell, RA, Fu, XY, Wrana, JL, Hogan, BLM & Ghosh, S 2003, 'Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis', Genes and Development, vol. 17, no. 23, pp. 2933-2949. https://doi.org/10.1101/gad.1145603
Xiao C, Shim JH, Klüppel M, Zhang SSM, Dong C, Flavell RA et al. Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis. Genes and Development. 2003 Dec 1;17(23):2933-2949. https://doi.org/10.1101/gad.1145603
Xiao, Changchun ; Shim, Jae Hyuck ; Klüppel, Michael ; Zhang, Samuel Shao Min ; Dong, Chen ; Flavell, Richard A. ; Fu, Xin Yuan ; Wrana, Jeffrey L. ; Hogan, Brigid L M ; Ghosh, Sankar. / Ecsit is required for Bmp signaling and mesoderm formation during mouse embryogenesis. In: Genes and Development. 2003 ; Vol. 17, No. 23. pp. 2933-2949.
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