Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin

Kunimasa Ohta; Giuseppe Lupo; Sei Kuriyama; Roger Keynes; Christine E. Holt; William A. Harris; Hideaki Tanaka; Shin Ichi Ohnuma

doi:10.1016/j.devcel.2004.08.014

Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin

Kunimasa Ohta, Giuseppe Lupo, Sei Kuriyama, Roger Keynes, Christine E. Holt, William A. Harris, Hideaki Tanaka, Shin Ichi Ohnuma

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

88 Citations (Scopus)

Abstract

During chick gastrulation, inhibition of BMP signaling is required for primitive streak formation and induction of Hensen's node. We have identified a unique secreted protein, Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family and is expressed in the primitive streak and Hensen's node. Grafts of cells expressing TSK in combination with the middle primitive streak induce an ectopic Hensen's node, while electroporation of TSK siRNA inhibits in-duction of the node. In Xenopus embryos, TSK can block BMP function and induce a secondary dorsal axis, while it can dorsalize ventral mesoderm and induce neural tissue in embryonic explants. Biochemical analysis shows that TSK binds directly to both BMP and chordin and forms a ternary complex with them. These observations indicate that TSK is an essential dorsalizing factor involved in the induction of Hensen's node.

Original language	English
Pages (from-to)	347-358
Number of pages	12
Journal	Developmental Cell
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.devcel.2004.08.014
Publication status	Published - Sept 2004
Externally published	Yes

All Science Journal Classification (ASJC) codes

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

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10.1016/j.devcel.2004.08.014

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@article{d0be50da75164548a1baeb176c2bfa47,

title = "Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin",

abstract = "During chick gastrulation, inhibition of BMP signaling is required for primitive streak formation and induction of Hensen's node. We have identified a unique secreted protein, Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family and is expressed in the primitive streak and Hensen's node. Grafts of cells expressing TSK in combination with the middle primitive streak induce an ectopic Hensen's node, while electroporation of TSK siRNA inhibits in-duction of the node. In Xenopus embryos, TSK can block BMP function and induce a secondary dorsal axis, while it can dorsalize ventral mesoderm and induce neural tissue in embryonic explants. Biochemical analysis shows that TSK binds directly to both BMP and chordin and forms a ternary complex with them. These observations indicate that TSK is an essential dorsalizing factor involved in the induction of Hensen's node.",

author = "Kunimasa Ohta and Giuseppe Lupo and Sei Kuriyama and Roger Keynes and Holt, {Christine E.} and Harris, {William A.} and Hideaki Tanaka and Ohnuma, {Shin Ichi}",

note = "Funding Information: We thank Jane Dodd, Jan Kitajewski, Richard Harland, and Akira Kurisaki for reagents, Kumiko Hori for help with chick embryos, Charles Kimmel, Robert Vignali, Linda Ko Ferrigno, Claudio Stern, Toshio Suda, and Takeshi Naruse for valuable advice and comments, and all members of our labs for valuable help. This work was supported by PRESTO of the Japan Science and Technology Agency (K.O.) and Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (K.O., H.T.), by the Cancer Research UK Senior Cancer Research Fellowship and MRC (S.-i.O.), by the Wellcome Trust and EC (W.A.H., C.E.H.), by an EMBO long-term postdoctoral fellowship (G.L.), and by 21 st Century COE Research (S.K., H.T.). Some of this work is included in patent application number GB224436.6 filed with Cambridge University Technical Services Limited. ",

year = "2004",

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doi = "10.1016/j.devcel.2004.08.014",

language = "English",

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T1 - Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin

AU - Ohta, Kunimasa

AU - Lupo, Giuseppe

AU - Kuriyama, Sei

AU - Keynes, Roger

AU - Holt, Christine E.

AU - Harris, William A.

AU - Tanaka, Hideaki

AU - Ohnuma, Shin Ichi

N1 - Funding Information: We thank Jane Dodd, Jan Kitajewski, Richard Harland, and Akira Kurisaki for reagents, Kumiko Hori for help with chick embryos, Charles Kimmel, Robert Vignali, Linda Ko Ferrigno, Claudio Stern, Toshio Suda, and Takeshi Naruse for valuable advice and comments, and all members of our labs for valuable help. This work was supported by PRESTO of the Japan Science and Technology Agency (K.O.) and Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (K.O., H.T.), by the Cancer Research UK Senior Cancer Research Fellowship and MRC (S.-i.O.), by the Wellcome Trust and EC (W.A.H., C.E.H.), by an EMBO long-term postdoctoral fellowship (G.L.), and by 21 st Century COE Research (S.K., H.T.). Some of this work is included in patent application number GB224436.6 filed with Cambridge University Technical Services Limited.

PY - 2004/9

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N2 - During chick gastrulation, inhibition of BMP signaling is required for primitive streak formation and induction of Hensen's node. We have identified a unique secreted protein, Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family and is expressed in the primitive streak and Hensen's node. Grafts of cells expressing TSK in combination with the middle primitive streak induce an ectopic Hensen's node, while electroporation of TSK siRNA inhibits in-duction of the node. In Xenopus embryos, TSK can block BMP function and induce a secondary dorsal axis, while it can dorsalize ventral mesoderm and induce neural tissue in embryonic explants. Biochemical analysis shows that TSK binds directly to both BMP and chordin and forms a ternary complex with them. These observations indicate that TSK is an essential dorsalizing factor involved in the induction of Hensen's node.

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ER -

Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin

Abstract

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