Diffusion of Nodal Signaling Activity in the Absence of the Feedback Inhibitor Lefty2

Chikara Meno; Jun Takeuchi; Rui Sakuma; Kazuko Koshiba-Takeuchi; Sachiko Ohishi; Yukio Saijoh; Jun Ichi Miyazaki; Peter Ten Dijke; Toshihiko Ogura; Hiroshi Hamada

doi:10.1016/S1534-5807(01)00006-5

Diffusion of Nodal Signaling Activity in the Absence of the Feedback Inhibitor Lefty2

Chikara Meno, Jun Takeuchi, Rui Sakuma, Kazuko Koshiba-Takeuchi, Sachiko Ohishi, Yukio Saijoh, Jun Ichi Miyazaki, Peter Ten Dijke, Toshihiko Ogura, Hiroshi Hamada

Research output: Contribution to journal › Article › peer-review

111 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	127-138
Number of pages	12
Journal	Developmental cell
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/S1534-5807(01)00006-5
Publication status	Published - 2001 Jul
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Developmental Biology
Cell Biology

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@article{63fb824bdc1546ef87931042b762dd73,

title = "Diffusion of Nodal Signaling Activity in the Absence of the Feedback Inhibitor Lefty2",

abstract = "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.",

author = "Chikara Meno and Jun Takeuchi and Rui Sakuma and Kazuko Koshiba-Takeuchi and Sachiko Ohishi and Yukio Saijoh and Miyazaki, {Jun Ichi} and {Ten Dijke}, Peter and Toshihiko Ogura and Hiroshi Hamada",

note = "Funding Information: We thank E. Robertson for nodal lacZ mice, T. Tabata for suggestions on the Smads antibody, and H. Hashiguchi for technical assistance. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan (to C.M., J.M., Y.S., T.O., and H.H.) and by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (to H.H.).",

year = "2001",

month = jul,

doi = "10.1016/S1534-5807(01)00006-5",

language = "English",

volume = "1",

pages = "127--138",

journal = "Developmental Cell",

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T1 - Diffusion of Nodal Signaling Activity in the Absence of the Feedback Inhibitor Lefty2

AU - Meno, Chikara

AU - Takeuchi, Jun

AU - Sakuma, Rui

AU - Koshiba-Takeuchi, Kazuko

AU - Ohishi, Sachiko

AU - Saijoh, Yukio

AU - Miyazaki, Jun Ichi

AU - Ten Dijke, Peter

AU - Ogura, Toshihiko

AU - Hamada, Hiroshi

N1 - Funding Information: We thank E. Robertson for nodal lacZ mice, T. Tabata for suggestions on the Smads antibody, and H. Hashiguchi for technical assistance. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan (to C.M., J.M., Y.S., T.O., and H.H.) and by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (to H.H.).

PY - 2001/7

Y1 - 2001/7

N2 - 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.

AB - 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.

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Diffusion of Nodal Signaling Activity in the Absence of the Feedback Inhibitor Lefty2

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