Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2

Yukio Saijoh; Hitoshi Adachi; Rui Sakuma; Chang Yeol Yeo; Kenta Yashiro; Minoru Watanabe; Hiromi Hashiguchi; Kyoko Mochida; Sachiko Ohishi; Masahiro Kawabata; Kohei Miyazono; Malcolm Whitman; Hiroshi Hamada

doi:10.1016/S1097-2765(00)80401-3

Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2

Yukio Saijoh, Hitoshi Adachi, Rui Sakuma, Chang Yeol Yeo, Kenta Yashiro, Minoru Watanabe, Hiromi Hashiguchi, Kyoko Mochida, Sachiko Ohishi, Masahiro Kawabata, Kohei Miyazono, Malcolm Whitman, Hiroshi Hamada

Department of Life Science

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

206 Scopus citations

Abstract

The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGFβ and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGFβ and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGFβ-related factor, which is most likely Nodal itself.

Original language	English
Pages (from-to)	35-47
Number of pages	13
Journal	Molecular Cell
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/S1097-2765(00)80401-3
State	Published - Jan 2000

Bibliographical note

Funding Information:
We thank M. Shen and A. Schier for mouse Cripto and Cryptic cDNA clones; Y. Eto for recombinant activin protein and activin cDNA; N. Ueno for BMP4 cDNA; C. Meno for nodal cDNA; A. Joyner and J. Rossant for hsp68lacZpA; T. Yokoyama and P. Overbeek for inv +/− mice; M. Brueckner for information on iv genotyping; and T. Miyama and T. Tanabe for technical assistance. We also thank E. Robertson and C. Wright for suggestions during the course of this work. This work was supported by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (to H. Hamada), by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to H. Hamada, K. Miyazono, and Y. Saijoh), by the Uehara Memorial Foundation (to Y. Saijoh), and by grants from NIH (to M. Whitman).

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Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C. Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Mochida, K., Ohishi, S., Kawabata, M., Miyazono, K., Whitman, M., & Hamada, H. (2000). Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. Molecular Cell, 5(1), 35-47. https://doi.org/10.1016/S1097-2765(00)80401-3

@article{ec969c002d4842ab9bc1ac94c503a5d0,

title = "Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2",

abstract = "The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGFβ and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGFβ and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGFβ-related factor, which is most likely Nodal itself.",

author = "Yukio Saijoh and Hitoshi Adachi and Rui Sakuma and Yeo, {Chang Yeol} and Kenta Yashiro and Minoru Watanabe and Hiromi Hashiguchi and Kyoko Mochida and Sachiko Ohishi and Masahiro Kawabata and Kohei Miyazono and Malcolm Whitman and Hiroshi Hamada",

note = "Funding Information: We thank M. Shen and A. Schier for mouse Cripto and Cryptic cDNA clones; Y. Eto for recombinant activin protein and activin cDNA; N. Ueno for BMP4 cDNA; C. Meno for nodal cDNA; A. Joyner and J. Rossant for hsp68lacZpA; T. Yokoyama and P. Overbeek for inv +/− mice; M. Brueckner for information on iv genotyping; and T. Miyama and T. Tanabe for technical assistance. We also thank E. Robertson and C. Wright for suggestions during the course of this work. This work was supported by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (to H. Hamada), by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to H. Hamada, K. Miyazono, and Y. Saijoh), by the Uehara Memorial Foundation (to Y. Saijoh), and by grants from NIH (to M. Whitman).",

year = "2000",

month = jan,

doi = "10.1016/S1097-2765(00)80401-3",

language = "English",

volume = "5",

pages = "35--47",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

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Saijoh, Y, Adachi, H, Sakuma, R, Yeo, CY, Yashiro, K, Watanabe, M, Hashiguchi, H, Mochida, K, Ohishi, S, Kawabata, M, Miyazono, K, Whitman, M & Hamada, H 2000, 'Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2', Molecular Cell, vol. 5, no. 1, pp. 35-47. https://doi.org/10.1016/S1097-2765(00)80401-3

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T1 - Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2

AU - Saijoh, Yukio

AU - Adachi, Hitoshi

AU - Sakuma, Rui

AU - Yeo, Chang Yeol

AU - Yashiro, Kenta

AU - Watanabe, Minoru

AU - Hashiguchi, Hiromi

AU - Mochida, Kyoko

AU - Ohishi, Sachiko

AU - Kawabata, Masahiro

AU - Miyazono, Kohei

AU - Whitman, Malcolm

AU - Hamada, Hiroshi

N1 - Funding Information: We thank M. Shen and A. Schier for mouse Cripto and Cryptic cDNA clones; Y. Eto for recombinant activin protein and activin cDNA; N. Ueno for BMP4 cDNA; C. Meno for nodal cDNA; A. Joyner and J. Rossant for hsp68lacZpA; T. Yokoyama and P. Overbeek for inv +/− mice; M. Brueckner for information on iv genotyping; and T. Miyama and T. Tanabe for technical assistance. We also thank E. Robertson and C. Wright for suggestions during the course of this work. This work was supported by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (to H. Hamada), by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to H. Hamada, K. Miyazono, and Y. Saijoh), by the Uehara Memorial Foundation (to Y. Saijoh), and by grants from NIH (to M. Whitman).

PY - 2000/1

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N2 - The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGFβ and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGFβ and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGFβ-related factor, which is most likely Nodal itself.

AB - The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGFβ and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGFβ and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGFβ-related factor, which is most likely Nodal itself.

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DO - 10.1016/S1097-2765(00)80401-3

M3 - Article

C2 - 10678167

AN - SCOPUS:0033969935

SN - 1097-2765

VL - 5

SP - 35

EP - 47

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -

Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2

Abstract

Bibliographical note

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