ArticleGenes & development2011
The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- Proprotein convertase activity regulates cumulus-oocyte-complex matrix integrity and cumulus cell migration during ovulation via a GDF9-dependent mechanism.bioRxiv : the preprint server for biology · 2026Article
- Review
- Stepwise release of Activin-A from its inhibitory prodomain is modulated by cysteines and requires furin coexpression to promote melanoma growth.Communications biology · 2024Article
- The Trophoblast Compartment Helps Maintain Embryonic Pluripotency and Delays Differentiation towards Cardiomyocytes.International journal of molecular sciences · 2023Article
- Stepwise pluripotency transitions in mouse stem cells.EMBO reports · 2022Review
- Review
- Deciphering epiblast lumenogenesis reveals proamniotic cavity control of embryo growth and patterning.Science advances · 2021Article
- Mouse embryo geometry drives formation of robust signaling gradients through receptor localization.Nature communications · 2019Article
- NODAL Secures Pluripotency upon Embryonic Stem Cell Progression from the Ground State.Stem cell reports · 2017Article
- A Molecular Sensor To Characterize Arenavirus Envelope Glycoprotein Cleavage by Subtilisin Kexin Isozyme 1/Site 1 Protease.Journal of virology · 2016Article
- Visualization of the Epiblast and Visceral Endodermal Cells Using Fgf5-P2A-Venus BAC Transgenic Mice and Epiblast Stem Cells.PloS one · 2016Article
- PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation.The Journal of cell biology · 2015Article
- Ectopically expressed pro-group X secretory phospholipase A2 is proteolytically activated in mouse adrenal cells by furin-like proprotein convertases: implications for the regulation of adrenal steroidogenesis.The Journal of biological chemistry · 2015Article
- Sonic hedgehog through Gli2 and Gli3 is required for the proper development of placental labyrinth.Cell death & disease · 2015Article
- Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a).The Journal of biological chemistry · 2013Article
- The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions.The Journal of biological chemistry · 2013Review
- The polybasic insertion in autotaxin α confers specific binding to heparin and cell surface heparan sulfate proteoglycans.The Journal of biological chemistry · 2013Article
- Ets2-dependent trophoblast signalling is required for gastrulation progression after primitive streak initiation.Nature communications · 2013Article
- The biology and therapeutic targeting of the proprotein convertases.Nature reviews. Drug discovery · 2012Review
- Probing embryonic stem cell autocrine and paracrine signaling using microfluidics.Annual review of analytical chemistry (Palo Alto, Calif.) · 2012Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fate of pluripotent cells in early mouse embryos is controlled by graded Nodal signals that are activated by the endoproteases Furin and Pace4. Soluble forms of Furin and Pace4 cleave proNodal in vitro and after secretion in transfected cells, but direct evidence for paracrine activity in vivo is elusive. Here, we show that Furin and Pace4 are released by the extraembryonic microenvironment, and that they cleave a membrane-bound reporter substrate in adjacent epiblast cells and activate Nodal to maintain pluripotency. Secreted Pace4 and Furin also stimulated mesoderm formation, whereas endoderm was only induced by Pace4, correlating with a difference in the spatiotemporal distribution of these proteolytic activities. Our analysis of paracrine Furin and Pace4 activities and their in vivo functions significantly advances our understanding of how the epiblast is patterned by its microenvironment. Adding cell-cell communication to the pleiotropic portfolio of these proteases provides a new framework to study proprotein processing also in other relevant contexts.
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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.