Evidence map›Paper›PMID 25373905›Full record

ArticleCell reports2014

ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation of FGF-SHH signaling.

Karen Handschuh, Jennifer Feenstra, Matthew Koss, Elisabetta Ferretti, Maurizio Risolino, Rediet Zewdu, Michelle A Sahai, Jean-Denis Bénazet, Xiao P Peng, Michael J Depew and 12 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 26% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Hedgehog Signal and Genetic Disorders.Frontiers in genetics · 2019
    Review
  5. Review
  6. Article
  7. ESCRTs are everywhere.The EMBO journal · 2015
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 4 countries.

Karen HandschuhDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Jennifer FeenstraDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Matthew KossDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Elisabetta FerrettiDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Maurizio RisolinoDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Rediet ZewduDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Michelle A SahaiDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
Jean-Denis BénazetDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Xiao P PengDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
Michael J DepewDepartment of Craniofacial Development, King's College London, Guy's Hospital, London Bridge, London SE1 9RT, UK; Department of Othopaedic Surgery, UCSF, San Francisco, CA 94110, USA.
Laura QuintanaDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA; Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain.
James SharpeCentre for Genomic Regulation (CRG), 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain; Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Spain.
Baolin WangDepartment of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Heather AlcornDevelopmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Roberta RiviDevelopmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Stephen ButcherDepartments of Biology and Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
J Robert ManakDepartments of Biology and Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
Thomas VaccariIFOM-FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Harel WeinsteinDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
Kathryn V AndersonDevelopmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Elizabeth LacyDevelopmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Licia SelleriDepartment of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: lis2008@med.cornell.edu.
Cornell University · USKettering University · USCentre for Genomic Regulation · ESUniversity of Iowa · USFIRC Institute of Molecular Oncology · ITGuy's Hospital · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
High-throughput targeted mutagenesis of mouse stem cell linesU01HG004080 · NHGRI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI DE JONG, PIETER J. · 2006 to 2010
$28.1M
Production of Targeted Null Mutations for 10,000 Genes in C57BL/6 ES CellsU01HG004085 · NHGRI · REGENERON PHARMACEUTICALS, INC. · PI VALENZUELA, DAVID MANUEL · 2006 to 2010
$25.3M
UCD KOMP PROJECT REPOSITORYU42RR024244 · NCRR · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LLOYD, KC KENT · 2007 to 2010
$7.9M
Isolation of Novel Mutations Affecting the Mouse EmbryoR37HD035455 · NICHD · SLOAN-KETTERING INST CAN RESEARCH · PI ANDERSON, KATHRYN V · 2008 to 2017
$6.9M
Mechanisms of Pbx-directed Genetic &Transcriptional Control of Limb DevelopmentR01HD043997 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI SELLERI, LICIA · 2004 to 2016
$3.7M
CLONING OF THE Hol MUTATIONR21DE018031 · NIDCR · WEILL MEDICAL COLL OF CORNELL UNIV · PI SELLERI, LICIA · 2008 to 2009
$573k
NCI NIH HHS P30 CA008748NCRR NIH HHS U42 RR024244NCRR NIH HHS U42RR024244NHGRI NIH HHS U01 HG004080NHGRI NIH HHS U01HG004080NHGRI NIH HHS U01 HG004085NHGRI NIH HHS U01HG004085NICHD NIH HHS 2R01HD043997NICHD NIH HHS R01 HD043997NICHD NIH HHS R37 HD035455NIDCR NIH HHS R21 DE018031NIDCR NIH HHS R21DE018031NIDCR NIH HHS R21DE018031-02S1NIGMS NIH HHS T32 GM007739
6 · The paper itself

Abstract

Sorting and degradation of receptors and associated signaling molecules maintain homeostasis of conserved signaling pathways during cell specification and tissue development. Yet, whether machineries that sort signaling proteins act preferentially on different receptors and ligands in different contexts remains mysterious. Here, we show that Vacuolar protein sorting 25, Vps25, a component of ESCRT-II (Endosomal Sorting Complex Required for Transport II), directs preferential endosome-mediated modulation of FGF signaling in limbs. By ENU-induced mutagenesis, we isolated a polydactylous mouse line carrying a hypomorphic mutation of Vps25 (Vps25(ENU)). Unlike Vps25-null embryos we generated, Vps25(ENU/ENU) mutants survive until late gestation. Their limbs display FGF signaling enhancement and consequent hyperactivation of the FGF-SHH feedback loop causing polydactyly, whereas WNT and BMP signaling remain unperturbed. Notably, Vps25(ENU/ENU) Mouse Embryonic Fibroblasts exhibit aberrant FGFR trafficking and degradation; however, SHH signaling is unperturbed. These studies establish that the ESCRT-II machinery selectively limits FGF signaling in vertebrate skeletal patterning.

Indexed as

Signal TransductionAnimalsEndosomal Sorting Complexes Required for TransportEndosomesExtremitiesFeedback, PhysiologicalFibroblast Growth FactorsFibroblastsHedgehog ProteinsMiceMice, Inbred C57BLMutationPolydactylyVesicular Transport ProteinsEndosomal Sorting Complexes Required for TransportFibroblast Growth FactorsHedgehog ProteinsShh protein, mousevacuolar protein sorting 25 protein, mouseVesicular Transport Proteins

Identifiers

PMID25373905
PMCPMC4223648
OpenAlexW2036001679

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.