Mouse lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation

Chikara Meno, Kira Gritsman, Sachiko Ohishi, Yasuhisa Ohfuji, Elizabeth Heckscher, Kyoko Mochida, Akihiko Shimono, Hisato Kondoh, William S. Talbot, Elizabeth J. Robertson, Alexander F. Schier, Hiroshi Hamada

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298 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)287-298
Number of pages12
JournalMolecular Cell
Volume4
Issue number3
DOIs
StatePublished - Sep 1999

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Meno, C., Gritsman, K., Ohishi, S., Ohfuji, Y., Heckscher, E., Mochida, K., Shimono, A., Kondoh, H., Talbot, W. S., Robertson, E. J., Schier, A. F., & Hamada, H. (1999). Mouse lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. Molecular Cell, 4(3), 287-298. https://doi.org/10.1016/S1097-2765(00)80331-7