Evidence map›Paper›PMID 40581929›Full record

ArticleCell reports2025

A live-cell biosensor of in vivo receptor tyrosine kinase activity reveals feedback regulation of a developmental gradient.

Emily K Ho, Rebecca P Kim-Yip, Alison G Simpkins, Payam E Farahani, Harrison R Oatman, Eszter Posfai, Stanislav Y Shvartsman, Jared E Toettcher

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. The regulatory logic of a dose-dependent developmental fate decision.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

  • Update of
    2025
5 · Who and what money

Authors and funding

8 authors.

Emily K HoDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: ekho@princeton.edu.
Rebecca P Kim-YipDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Alison G SimpkinsLewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Payam E FarahaniDepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Harrison R OatmanLewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Eszter PosfaiDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Stanislav Y ShvartsmanDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Center for Computational Biology, Flatiron Institute - Simons Foundation, New York, NY 10010, USA.
Jared E ToettcherDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, NJ 08544, USA. Electronic address: toettcher@princeton.edu.

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Cale Whitworth · 2014 to 2026
$13.5M
Control of the 4D chromatin landscape underlying gene activity during developmentU01DK127429 · NIDDK · PRINCETON UNIVERSITY · PI GREGOR, THOMAS, LEVINE, MICHAEL STEVEN · 2020 to 2024
$3.2M
Collective dynamics in cell clustersR01GM134204 · NIGMS · PRINCETON UNIVERSITY · PI Stanislav Y. Shvartsman · 2019 to 2026
$2.6M
NRSA TrainingTL1TR003019 · NCATS · RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS · PI SCOTTO, KATHLEEN W. · 2019 to 2023
$1.9M
Mechanisms of signal integration in developmental control of organ size and tissue patterningR01HD085870 · NICHD · UNIVERSITY OF MASSACHUSETTS BOSTON · PI VERAKSA, ALEXEY · 2016 to 2020
$1.6M
A new class of biosensors for detecting signaling dynamics without live-cell microscopyR01GM144362 · NIGMS · PRINCETON UNIVERSITY · PI TOETTCHER, JARED E · 2022 to 2025
$1.3M
Mechanisms of signal integration in developmental control of organ size and tissue patterningR01GM141843 · NIGMS · UNIVERSITY OF MASSACHUSETTS BOSTON · PI VERAKSA, ALEXEY · 2021 to 2024
$1.2M
Optogenetic dissection of Erk signal interpretation in early embryogenesisF32GM148016 · NIGMS · PRINCETON UNIVERSITY · PI HO, EMILY KOLENBRANDER · 2023 to 2024
$146k
NCATS NIH HHS TL1 TR003019NICHD NIH HHS R01 HD085870NIDDK NIH HHS U01 DK127429NIGMS NIH HHS F32 GM148016NIGMS NIH HHS R01 GM134204NIGMS NIH HHS R01 GM141843NIGMS NIH HHS R01 GM144362NIH HHS P40 OD018537
6 · The paper itself

Abstract

A lack of tools for detecting receptor activity in vivo has limited our ability to fully explore receptor-level control of developmental patterning. Here, we extend phospho-tyrosine tag (pYtag) biosensors to visualize endogenous receptor tyrosine kinase (RTK) activity in Drosophila. We build biosensors for three RTKs that function across developmental stages and tissues. By characterizing Torso::pYtag during embryonic terminal patterning, we find that Torso activity differs from downstream extracellular signal-regulated kinase (ERK) activity in two surprising ways: Torso activity is narrowly restricted to the poles but produces a broader gradient of ERK and decreases over developmental time, while ERK activity is sustained, an effect mediated by ERK pathway-dependent negative feedback. Our results suggest that a narrow domain of Torso activity, tuned in amplitude by negative feedback, locally activates signaling effectors, which diffuse through the syncytial embryo to form the ERK gradient. Altogether, the results of this work highlight the usefulness of pYtags for investigating receptor-level regulation of developmental patterning.

Indexed as

Biosensing TechniquesDrosophila melanogasterDrosophila ProteinsFeedback, PhysiologicalReceptor Protein-Tyrosine KinasesAnimalsBody PatterningExtracellular Signal-Regulated MAP KinasesMAP Kinase Signaling SystemSignal TransductionDrosophila ProteinsExtracellular Signal-Regulated MAP KinasesReceptor Protein-Tyrosine KinasesbiosensorCP: Cell biologyCP: Developmental biologyDrosophila developmentERK signalingreceptor tyrosine kinases

Identifiers

PMID40581929
PMCPMC12356409

What OpenQuestion holds

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Registered trials

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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.