Mouse Lefty2 and Zebrafish Antivin Are Feedback Inhibitors of Nodal Signaling during Vertebrate Gastrulation
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
EPI descendants resembled embryonic VE (emVE) and anterior visceral endoderm (AVE), based on expression of markers including Lefty1, Cer1 and Hhex.
“Expression of markers of embryonic (em)VE, and anterior visceral endoderm (AVE), a specialized cellular cohort of emVE exhibiting an intra-epithelial, distal-to-anterior migratory behavior between E5.5 and E6.0, including Lefty1, Cer1 and Hhex30–32, suggested these EPI descendants resembled emVE and AVE (Fig. 2c, Extended Data Fig. 6e)33.”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [31]
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 45 · Cited by 374
- Authors
- 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.
- Affiliations
- The University of Osaka (JP)
- NYU Langone Health (US)
- Japan Science and Technology Agency (JP)
- Harvard University (US)
- Corresponding author
- Hamada, Hiroshi
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 1999-09
- Volume
- 4
- Issue
- 3
- Pages
- 287-298
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2092088384
- Cited by
- 374
- References
- 45
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 13 · 2021: 5 · 2020: 12 · 2019: 10 · 2018: 14 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 6 · 2013: 10 · 2012: 15
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Core Research for Evolutional Science and Technology
- National Institutes of Health
- Japan Science and Technology Corporation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- LEFTY2, Nodal signaling, product inhibition, gastrulation, TGF-beta superfamily, mesoderm formation, primitive streak, Cyclops, strabismus, ActRIIB, zebrafish, mouse mutants
- MeSH terms
- Animals, Feedback, Gastrula, Genes, Lethal, Heterozygote, Histocytochemistry, Mesoderm, Mice, Mutant Strains, Phenotype, RNA, Messenger, Zebrafish, Signal Transduction, Transforming Growth Factor beta, Mutagenesis, In Situ Hybridization, Receptors, Growth Factor, Gene Expression Regulation, Developmental, Body Patterning, Zebrafish Proteins, Activin Receptors, Type II, Mice, Nodal Protein, Left-Right Determination Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
