Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer

  1. Hitoshi Adachi,
  2. Yukio Saijoh,
  3. Kyoko Mochida,
  4. Sachiko Ohishi,
  5. Hiromi Hashiguchi,
  6. Akiko Hirao, and
  7. Hiroshi Hamada
  1. Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Suita, Osaka 565, Japan; and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST)

Abstract

The nodal gene is expressed on the left side of developing mouse embryos and is implicated in left/right (L-R) axis formation. The transcriptional regulatory regions of nodal have now been investigated by transgenic analysis. A node-specific enhancer was detected in the upstream region (−9.5 to −8.7 kb) of the gene. Intron 1 was also shown to contain a left side-specific enhancer (ASE) that was able to direct transgene expression in the lateral plate mesoderm and prospective floor plate on the left side. A 3.5-kb region of nodal that contained ASE responded to mutations iniv, inv, and lefty-1, all genes that act upstream of nodal. The same 3.5- kb region also directed expression in the epiblast and visceral endoderm at earlier stages of development. Characterization of deletion constructs delineated ASE to a 340-bp region that was both essential and sufficient for asymmetric expression of nodal. Several sequence motifs were found to be conserved between the nodal ASE and the lefty-2 ASE, some of which appeared to be essential for nodal ASE activity. These results suggest that similar transcriptional mechanisms underlie the asymmetric expression of nodal and of lefty-2 as well as the earlier expression of nodal in the epiblast and endoderm.

Keywords

Footnotes

  • Corresponding author.

  • E-MAIL hamada{at}imcb.osaka-u.ac.jp; FAX 81-6-878-9846.

    • Received April 17, 1999.
    • Accepted May 10, 1999.
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