ZFIN ID: ZDB-PUB-991020-11
Mouse lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation
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., and Hamada, H.
Date: 1999
Source: Molecular Cell   4(3): 287-298 (Journal)
Registered Authors: Gritsman, Kira, Heckscher, Ellie, Kondoh, Hisato, Schier, Alexander, Talbot, William S.
Keywords: none
MeSH Terms:
  • Activin Receptors, Type II
  • Animals
  • Body Patterning*
  • Feedback
  • Gastrula/physiology*
  • Gene Expression Regulation, Developmental
  • Genes, Lethal
  • Heterozygote
  • Histocytochemistry
  • In Situ Hybridization
  • Left-Right Determination Factors
  • Mesoderm
  • Mice/embryology*
  • Mice, Mutant Strains
  • Mutagenesis
  • Nodal Protein
  • Phenotype
  • RNA, Messenger
  • Receptors, Growth Factor/metabolism
  • Signal Transduction
  • Transforming Growth Factor beta/antagonists & inhibitors
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish Proteins*
PubMed: 10518210 Full text @ Mol. Cell
Mammalian lefty and zebrafish antivin form a subgroup of the TGF beta 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 TGF beta 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.