Activin/Nodal responsiveness and asymmetric expression of a Xenopus nodal-related gene converge on a FAST-regulated module in intron 1

Shin Ichi Osada, Yukio Saijoh, Amanda Frisch, Chang Yeol Yeo, Hitoshi Adachi, Minoru Watanabe, Malcolm Whitman, Hiroshi Hamada, Christopher V.E. Wright

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Vertebrate Nodal-related factors play central roles in mesendoderm induction and left-right axis specification, but the mechanisms regulating their expression are largely unknown. We identify an element in Xnr1 intron 1 that is activated by activin and Vg1, autoactivated by Xnrs, and suppressed by ventral inducers like BMP4. Intron 1 contains three FAST binding sites on which FAST/Smad transcriptional complexes can assemble; these sites are differentially involved in intron 1-mediated reporter gene expression. Interference with FAST function abolishes intron 1 activity, and transcriptional activation of Xnrs by activin in embryonic tissue explant assays, identifying FAST as an essential mediator of Xnr autoregulation and/or 'signal relay' from activin-like molecules. Furthermore, the mapping of endogenous activators of the Xnr1 intronic enhancer within Xenopus embryos agrees well with the pattern of Xnr1 transcription during embryogenesis. In transgenic mice, Xnr1 intron 1 mimics a similarly located enhancer in the mouse nodal gene, and directs FAST site-dependent expression in the primitive streak during gastrulation, and unilateral expression during early somitogenesis. The FAST cassette is similar in an ascidian nodal-related gene, suggesting an ancient origin for this regulatory module. Thus, an evolutionarily conserved intronic enhancer in Xnr1 is involved in both mesendoderm induction and asymmetric expression during left-right axis formation.

Original languageEnglish
Pages (from-to)2503-2514
Number of pages12
JournalDevelopment
Volume127
Issue number11
StatePublished - Jun 2000

Keywords

  • Activin
  • FAST-1
  • Left-right asymmetry
  • Nodal
  • TGFβ
  • Xenopus

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