Evidence map›Paper›PMID 39610242›Full record

ArticleDevelopmental cell2025

The vertebrate segmentation clock drives segmentation by stabilizing Dusp phosphatases in zebrafish.

M Fethullah Simsek, Didar Saparov, Kemal Keseroglu, Oriana Zinani, Angad Singh Chandel, Bibek Dulal, Bal Krishan Sharma, Soling Zimik, Ertuğrul M Özbudak

Abstract read
In one paragraph

Article in Developmental cell, 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

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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. Article
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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

9 authors.

M Fethullah SimsekDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: mfsimsek@mcmaster.ca.
Didar SaparovDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Molecular and Developmental Biology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Kemal KeserogluDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Oriana ZinaniDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Molecular and Developmental Biology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Angad Singh ChandelDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Systems Biology and Physiology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Bibek DulalDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Physics, University of Cincinnati College of Arts and Sciences, Cincinnati, OH 45221, USA.
Bal Krishan SharmaCancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Soling ZimikDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Ertuğrul M ÖzbudakDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: ozbudak@northwestern.edu.

Funding

Integration of spatiotemporal signaling for pattern formation and scalingR01HD103623 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ertugrul M Ozbudak · 2021 to 2026
$2.4M
NICHD NIH HHS R01 HD103623
6 · The paper itself

Abstract

Pulsatile activity of the extracellular signal-regulated kinase (ERK) controls several cellular, developmental, and regenerative programs. Sequential segmentation of somites along the vertebrate body axis, a key developmental program, is also controlled by ERK activity oscillation. The oscillatory expression of Her/Hes family transcription factors constitutes the segmentation clock, setting the period of segmentation. Although oscillation of ERK activity depends on Her/Hes proteins, the underlying molecular mechanism remained mysterious. Here, we show that Her/Hes proteins physically interact with and stabilize dual-specificity phosphatases (Dusp) of ERK, resulting in oscillations of Dusp4 and Dusp6 proteins. Pharmaceutical and genetic inhibition of Dusp activity disrupt ERK activity oscillation and somite segmentation in zebrafish. Our results demonstrate that post-translational interactions of Her/Hes transcription factors with Dusp phosphatases establish the fundamental vertebrate body plan. We anticipate that future studies will identify currently unnoticed post-translational control of ERK pulses in other systems.

Indexed as

Body PatterningDual-Specificity PhosphatasesZebrafishZebrafish ProteinsAnimalsDual Specificity Phosphatase 6Extracellular Signal-Regulated MAP KinasesGene Expression Regulation, DevelopmentalMAP Kinase Signaling SystemSomitesDual Specificity Phosphatase 6Dual-Specificity PhosphatasesExtracellular Signal-Regulated MAP KinasesZebrafish ProteinsclockDuspERKoscillationpattern formationpost-translationalsegmentationsomitogenesiswave

Identifiers

PMID39610242
PMCPMC11903174

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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.