Diffusion of nodal signaling activity in the absence of the feedback inhibitor Lefty2.
The role of Lefty2 in left-right patterning was investigated by analysis of mutant mice that lack asymmetric expression of lefty2. These animals exhibited various situs defects including left isomerism. The asymmetric expression of nodal was prolonged and the expression of Pitx2 was upregulated in the mutant embryos. The absence of Lefty2 conferred on Nodal the ability to diffuse over a long distance. Thus, Nodal-responsive genes, including Pitx2, that are normally expressed on the left side were expressed bilaterally in the mutant embryos, even though nodal expression was confined to the left side. These results suggest that Nodal is a long-range signaling molecule but that its range of action is normally limited by the feedback inhibitor Lefty2.
Meno
C
C
Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Japan.
Takeuchi
J
J
Sakuma
R
R
Koshiba-Takeuchi
K
K
Ohishi
S
S
Saijoh
Y
Y
Miyazaki
J
J
ten Dijke
P
P
Ogura
T
T
Hamada
H
H
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004058:Diffusion; D025461:Feedback, Physiological / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D055458:Left-Right Determination Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055457:Nodal Protein; D009687:Nuclear Proteins; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D055458:Left-Right Determination Factors; D055457:Nodal Protein; D009687:Nuclear Proteins; D051899:Smad2 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097577:Homeobox Protein PITX2; C526008:Nodal protein, mouse; C497783:Smad2 protein, mouse