Evidence map›Paper›PMID 38574735›Full record

ArticleDevelopmental cell2024

Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain.

Lena Tveriakhina, Gustavo Scanavachi, Emily D Egan, Ricardo Bango Da Cunha Correia, Alexandre P Martin, Julia M Rogers, Jeremy S Yodh, Jon C Aster, Tom Kirchhausen, Stephen C Blacklow

Open access · greenAbstract read
In one paragraph

Article in Developmental cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025
    Review
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Lena TveriakhinaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Gustavo ScanavachiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Emily D EganDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Ricardo Bango Da Cunha CorreiaDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Alexandre P MartinDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Julia M RogersDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Jeremy S YodhDepartment of Physics, Harvard University, Cambridge, MA 02138, USA.
Jon C AsterDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Tom KirchhausenDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kirchhausen@crystal.harvard.edu.
Stephen C BlacklowDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: stephen_blacklow@hms.harvard.edu.
Harvard University · USBoston Children's Hospital · USBrigham and Women's Hospital · US

Funding

Notch Signaling in CancerR35CA220340 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2017 to 2023
$7.1M
VISUALIZATION OF SUBCELLULAR DYNAMICS IN MULTICELLULAR ORGANISMSR35GM130386 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI TOMAS KIRCHHAUSEN · 2019 to 2026
$4.0M
Dynamics of Notch SignalingR01CA272484 · NCI · HARVARD MEDICAL SCHOOL · PI Stephen C. Blacklow · 2022 to 2026
$3.3M
Dynamic mechanisms of transcriptional coactivator function in Notch signalingK99GM144750 · NIGMS · HARVARD MEDICAL SCHOOL · PI ROGERS, JULIA MARIA · 2022 to 2023
$222k
NCI NIH HHS R01 CA272484NCI NIH HHS R35 CA220340NIGMS NIH HHS K99 GM144750NIGMS NIH HHS R35 GM130386
6 · The paper itself

Abstract

Mammalian Notch signaling occurs when the binding of Delta or Jagged to Notch stimulates the proteolytic release of the Notch intracellular domain (NICD), which enters the nucleus to control target gene expression. To determine the temporal dynamics of events associated with Notch signaling under native conditions, we fluorescently tagged Notch and Delta at their endogenous genomic loci and visualized them upon pairing of receiver (Notch) and sender (Delta) cells as a function of time after cell contact. At contact sites, Notch and Delta immediately accumulated at 1:1 stoichiometry in synapses, which resolved by 15-20 min after contact. Synapse formation preceded the entrance of the Notch extracellular domain into the sender cell and accumulation of NICD in the nucleus of the receiver cell, which approached a maximum after ∼45 min and was prevented by chemical and genetic inhibitors of signaling. These findings directly link Notch-Delta synapse dynamics to NICD production with spatiotemporal precision.

Indexed as

Cell NucleusReceptors, NotchSignal TransductionSynapsesHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsProtein Domainsdelta proteinIntracellular Signaling Peptides and ProteinsMembrane ProteinsReceptors, NotchDeltadevelopmentNotchreceptorregulated proteolysissignaling dynamicssignal transductionsynapsestranscriptiontransendocytosis

Identifiers

PMID38574735
PMCPMC11153029
OpenAlexW4393899479

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.