In vivo convergence of BMP and MAPK signaling pathways: Impact of differential Smad1 phosphorylation on development and homeostasis

Josée Aubin, Alice Davy, Philippe Soriano

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Integration of diverse signaling pathways is essential in development and homeostasis for cells to interpret context-dependent cues. BMP and MAPK signaling converge on Smads, resulting in differential phosphorylation. To understand the physiological significance of this observation, we have generated Smad1 mutant mice carrying mutations that prevent phosphorylation of either the C-terminal motif required for BMP downstream transcriptional activation (Smad1C mutation) or of the MAPK motifs in the linker region (Smad1L mutation). Smad1C/C mutants recapitulate many Smad1-/- phenotypes, including defective allantois formation and the lack of primordial germ cells (PGC), but also show phenotypes that are both more severe (head and branchial arches) and less severe (allantois growth) than the null. Smad1L/L mutants survive embryogenesis but exhibit defects in gastric epithelial homeostasis correlated with changes in cell contacts, actin cytoskeleton remodeling, and nuclear β-catenin accumulation. In addition, formation of PGCs is impaired in Smad1L/L mutants, but restored by allelic complementation in Smad1C/L compound mutants. These results underscore the need to tightly balance BMP and MAPK signaling pathways through Smad1.

Original languageEnglish
Pages (from-to)1482-1494
Number of pages13
JournalGenes and Development
Volume18
Issue number12
DOIs
StatePublished - 15 Jun 2004
Externally publishedYes

Keywords

  • Germ line
  • Homeostasis
  • MAPK
  • Signaling
  • Smad
  • TGFβ

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