Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer.
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.
Adachi
H
H
Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Suita, Osaka 565, Japan.
Saijoh
Y
Y
Mochida
K
K
Ohishi
S
S
Hashiguchi
H
H
Hirao
A
A
Hamada
H
H
D000818:Animals; D019521:Body Patterning; D005314:Embryonic and Fetal Development; D004707:Endoderm; D004742:Enhancer Elements, Genetic; D005775:Gastrula; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007438:Introns; D055458:Left-Right Determination Factors; D051379:Mice; D016296:Mutagenesis; D055457:Nodal Protein; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D019076:Transgenes
C491947:Invs protein, mouse; D055458:Left-Right Determination Factors; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011506:Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta