TY - JOUR
T1 - Mouse lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation
AU - Meno, Chikara
AU - Gritsman, Kira
AU - Ohishi, Sachiko
AU - Ohfuji, Yasuhisa
AU - Heckscher, Elizabeth
AU - Mochida, Kyoko
AU - Shimono, Akihiko
AU - Kondoh, Hisato
AU - Talbot, William S.
AU - Robertson, Elizabeth J.
AU - Schier, Alexander F.
AU - Hamada, Hiroshi
N1 - Funding Information:
We thank R. Beddington, I. Dawid, S. Dougan, Y. Imai, G. Martin, B. Hermann, Y. Saga, H. Sasaki, S. Wilson, C. Wright, and B. and C. Thisse for sharing reagents used in this study; Y. Saijoh for his comments; and K. Miyama and T. Tanabe for their excellent technical assistance. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan (to H. H. and H. K.), by a grant from CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (to H. H.), and by grants from NIH (to A. F. S., W. S. T, and E. J. R.).
PY - 1999/9
Y1 - 1999/9
N2 - Mammalian lefty and zebrafish antivin form a subgroup of the TGFβ superfamily. We report that mouse mutants for lefty2 have an expanded primitive streak and form excess mesoderm, a phenotype opposite to that of mutants for the TGFβ gene nodal. Analogously, overexpression of Antivin or Lefty2 in zebrafish embryos blocks head and trunk mesoderm formation, a phenotype identical to that of mutants caused by loss of Nodal signaling. The lefty2 mutant phenotype is partially suppressed by heterozygosity for nodal. Similarly, the effects of Antivin and Lefty2 can be suppressed by overexpression of the nodal-related genes cyclops and squint or the extracellular domain of ActRIIB. Expression of antivin is dependent on Nodal signaling, revealing a feedback loop wherein Nodal signals induce their antagonists Lefty2 and Antivin to restrict Nodal signaling during gastrulation.
AB - Mammalian lefty and zebrafish antivin form a subgroup of the TGFβ superfamily. We report that mouse mutants for lefty2 have an expanded primitive streak and form excess mesoderm, a phenotype opposite to that of mutants for the TGFβ gene nodal. Analogously, overexpression of Antivin or Lefty2 in zebrafish embryos blocks head and trunk mesoderm formation, a phenotype identical to that of mutants caused by loss of Nodal signaling. The lefty2 mutant phenotype is partially suppressed by heterozygosity for nodal. Similarly, the effects of Antivin and Lefty2 can be suppressed by overexpression of the nodal-related genes cyclops and squint or the extracellular domain of ActRIIB. Expression of antivin is dependent on Nodal signaling, revealing a feedback loop wherein Nodal signals induce their antagonists Lefty2 and Antivin to restrict Nodal signaling during gastrulation.
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U2 - 10.1016/S1097-2765(00)80331-7
DO - 10.1016/S1097-2765(00)80331-7
M3 - Article
C2 - 10518210
AN - SCOPUS:0033197552
SN - 1097-2765
VL - 4
SP - 287
EP - 298
JO - Molecular Cell
JF - Molecular Cell
IS - 3
ER -