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

Genes Dev. 1999 Jun 15;13(12):1589-600. doi: 10.1101/gad.13.12.1589.

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 in iv, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Embryonic and Fetal Development
  • Endoderm
  • Enhancer Elements, Genetic*
  • Gastrula
  • Gene Expression
  • Gene Expression Regulation, Developmental*
  • Introns
  • Left-Right Determination Factors
  • Mice
  • Mutagenesis
  • Nodal Protein
  • Proteins / genetics
  • Transcription Factors*
  • Transforming Growth Factor beta / genetics*
  • Transgenes

Substances

  • Invs protein, mouse
  • Left-Right Determination Factors
  • Nodal Protein
  • Nodal protein, mouse
  • Proteins
  • Transcription Factors
  • Transforming Growth Factor beta