Role of asymmetric signals in left-right patterning in the mouse.
Left-right asymmetric signaling molecules in mammals include three transforming growth factor beta (TGFbeta)-related factors, Nodal, Lefty1 and Lefty2. They are all expressed on the left half of developing mouse embryos. Nodal acts as a left-side determinant by transducing signals through Smad and FAST and by inducing Pitx2 expression on the left side. Lefty proteins are antagonists that inhibit Nodal signaling. There are positive and negative transcriptional regulatory loops between nodal and lefty2 genes. Thus, Nodal activates its own gene and lefty2. Lefty2 protein produced then inhibits Nodal signaling and terminates expression of both genes. This feedback mechanism can restrict the range and duration of Nodal signaling in developing embryos.
Hamada
H
H
Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, and CREST Japan Science and Technology Corporation (JST), Osaka, Japan. hamada@imcb.osaka-u.ac.jp
Meno
C
C
Saijoh
Y
Y
Adachi
H
H
Yashiro
K
K
Sakuma
R
R
Shiratori
H
H
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics* / Q000503:physiopathology; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055458:Left-Right Determination Factors; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D055457:Nodal Protein; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics
D055458:Left-Right Determination Factors; D055457:Nodal Protein; C526008:Nodal protein, mouse; D016212:Transforming Growth Factor beta