ArticleProceedings of the National Academy of Sciences of the United States of America2013
Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 85 citations in OpenAlex.
- Sox8 is essential for vertebrate gastrulation.EMBO reports · 2025Article
- Chordin-mediated BMP shuttling patterns the secondary body axis in a cnidarian.Science advances · 2025Article
- The emergence ofFrontiers in cell and developmental biology · 2025Article
- Highly conserved and extremely evolvable: BMP signalling in secondary axis patterning of Cnidaria and Bilateria.Development genes and evolution · 2024Review
- Cell lineage-guided mass spectrometry reveals increased energy metabolism and reactive oxygen species in the vertebrate organizer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation.EMBO reports · 2024Article
- Reconstitution of morphogen shuttling circuits.Science advances · 2023Article
- The developmental gene Chordin is amplified and expressed in human cancers.Molecular & cellular oncology · 2023Article
- Pleiotropic functions of chordin gene causing drastic morphological changes in ornamental goldfish.Scientific reports · 2022Article
- Patterning principles of morphogen gradients.Open biology · 2022Review
- The Organizer and Its Signaling in Embryonic Development.Journal of developmental biology · 2021Review
- Optogenetic Control of the Canonical Wnt Signaling Pathway During Xenopus laevis Embryonic Development.Journal of molecular biology · 2021Article
- Generation of extracellular morphogen gradients: the case for diffusion.Nature reviews. Genetics · 2021Review
- Article
- Diversity and robustness of bone morphogenetic protein pattern formation.Development (Cambridge, England) · 2021Review
- Furry is required for cell movements during gastrulation and functionally interacts with NDR1.Scientific reports · 2021Article
- BMP Signaling: Lighting up the Way for Embryonic Dorsoventral Patterning.Frontiers in cell and developmental biology · 2021Review
- Article
- Proteolytic Restriction of Chordin Range Underlies BMP Gradient Formation.Cell reports · 2020Article
- Natural size variation among embryos leads to the corresponding scaling in gene expression.Developmental biology · 2020Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The vertebrate body plan follows stereotypical dorsal-ventral (D-V) tissue differentiation controlled by bone morphogenetic proteins (BMPs) and secreted BMP antagonists, such as Chordin. The three germ layers--ectoderm, mesoderm, and endoderm--are affected coordinately by the Chordin-BMP morphogen system. However, extracellular morphogen gradients of endogenous proteins have not been directly visualized in vertebrate embryos to date. In this study, we improved immunolocalization methods in Xenopus embryos and analyzed the distribution of endogenous Chordin using a specific antibody. Chordin protein secreted by the dorsal Spemann organizer was found to diffuse along a narrow region that separates the ectoderm from the anterior endoderm and mesoderm. This Fibronectin-rich extracellular matrix is called "Brachet's cleft" in the Xenopus gastrula and is present in all vertebrate embryos. Chordin protein formed a smooth gradient that encircled the embryo, reaching the ventral-most Brachet cleft. Depletion with morpholino oligos showed that this extracellular gradient was regulated by the Chordin protease Tolloid and its inhibitor Sizzled. The Chordin gradient, as well as the BMP signaling gradient, was self-regulating and, importantly, was able to rescale in dorsal half-embryos. Transplantation of Spemann organizer tissue showed that Chordin diffused over long distances along this signaling highway between the ectoderm and mesoderm. Chordin protein must reach very high concentrations in this narrow region. We suggest that as ectoderm and mesoderm undergo morphogenetic movements during gastrulation, cells in both germ layers read their positional information coordinately from a single morphogen gradient located in Brachet's cleft.
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