ArticleGenes & development2001
The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development.
Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 309 citations in OpenAlex.
- Optogenetic control of Nodal signaling patterns.Development (Cambridge, England) · 2025Article
- High-throughput transcriptome analysis reveals a developmental increase in Acvr1c which mediates epigenetic repression of the gene encoding the pubertal brake, Makorin ring finger protein 3.NAR molecular medicine · 2025Article
- Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.Protein science : a publication of the Protein Society · 2025Article
- Nodal and cripto-1: distinct functions regulate trophoblast specification in mouse pregnancy.Frontiers in cell and developmental biology · 2025Article
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- Maternal TGF-β ligand Panda breaks the radial symmetry of the sea urchin embryo by antagonizing the Nodal type II receptor ACVRII.PLoS biology · 2024Article
- Optogenetic control of Nodal signaling patterns.bioRxiv : the preprint server for biology · 2024Article
- Automated, High-Throughput Phenotypic Screening and Analysis Platform to Study Pre- and Post-Implantation Morphogenesis in Stem Cell-Derived Embryo-Like Structures.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hepatic Activin E mediates liver-adipose inter-organ communication, suppressing adipose lipolysis in response to elevated serum fatty acids.Molecular metabolism · 2023Article
- The Photoperiod Regulates Granulosa Cell Apoptosis through the FSH-Nodal/ALK7 Signaling Pathway inAnimals : an open access journal from MDPI · 2022Article
- Quantitative analysis of transcriptome dynamics provides novel insights into developmental state transitions.BMC genomics · 2022Article
- LncRNA-Smad7 mediates cross-talk between Nodal/TGF-β and BMP signaling to regulate cell fate determination of pluripotent and multipotent cells.Nucleic acids research · 2022Article
- Regulation of Nodal signaling propagation by receptor interactions and positive feedback.eLife · 2022Article
- YAP1 regulates the self-organized fate patterning of hESC-derived gastruloids.Stem cell reports · 2022Article
- TGF-β superfamily co-receptors in cancer.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Epstein-Barr virus microRNA BART10-3p promotes dedifferentiation and proliferation of nasopharyngeal carcinoma by targeting ALK7.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal.International journal of molecular sciences · 2021Review
- Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer.Biomedicines · 2021Review
- Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Nodal proteins have crucial roles in mesendoderm formation and left-right patterning during vertebrate development. The molecular mechanisms of signal transduction by Nodal and related ligands, however, are not fully understood. In this paper, we present biochemical and functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a receptor for mouse Nodal and Xenopus Nodal-related 1 (Xnr1). Receptor reconstitution experiments indicate that ALK7 collaborates with ActRIIB to confer responsiveness to Xnr1 and Nodal. Both receptors can independently bind Xnr1. In addition, Cripto, an extracellular protein genetically implicated in Nodal signaling, can independently interact with both Xnr1 and ALK7, and its expression greatly enhances the ability of ALK7 and ActRIIB to respond to Nodal ligands. The Activin receptor ALK4 is also able to mediate Nodal signaling but only in the presence of Cripto, with which it can also interact directly. A constitutively activated form of ALK7 mimics the mesendoderm-inducing activity of Xnr1 in Xenopus embryos, whereas a dominant-negative ALK7 specifically blocks the activities of Nodal and Xnr1 but has little effect on other related ligands. In contrast, a dominant-negative ALK4 blocks all mesoderm-inducing ligands tested, including Nodal, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a role in Nodal signaling, ALK7 mRNA is localized to the ectodermal and organizer regions of Xenopus gastrula embryos and is expressed during early stages of mouse embryonic development. Therefore, our results indicate that both ALK4 and ALK7 can mediate signal transduction by Nodal proteins, although ALK7 appears to be a receptor more specifically dedicated to Nodal signaling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.