Evidence map›Paper›PMID 36916392›Full record

ArticleDisease models & mechanisms2023

Dual mechanism underlying failure of neural tube closure in the Zic2 mutant mouse.

Sarah Escuin, Saba Rose Raza-Knight, Dawn Savery, Carles Gaston-Massuet, Gabriel L Galea, Nicholas D E Greene, Andrew J Copp

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. A computational dynamic systems model forCurrent research in toxicology · 2025
    Article
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

7 authors at 1 institution in 1 country.

Sarah EscuinDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Saba Rose Raza-KnightDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0001-6398-8173
Dawn SaveryDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Carles Gaston-MassuetDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0002-6793-3118
Gabriel L GaleaDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0003-2515-1342
Nicholas D E GreeneDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0002-4170-5248
Andrew J CoppDevelopmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.ORCID 0000-0002-2544-9117
University College London · GB

Funding

Medical Research Council G0801124University College LondonWellcome TrustWellcome Trust 087525
6 · The paper itself

Abstract

Understanding the molecular mechanisms that lead to birth defects is an important step towards improved primary prevention. Mouse embryos homozygous for the Kumba (Ku) mutant allele of Zic2 develop severe spina bifida with complete lack of dorsolateral hinge points (DLHPs) in the neuroepithelium. Bone morphogenetic protein (BMP) signalling is overactivated in Zic2Ku/Ku embryos, and the BMP inhibitor dorsomorphin partially rescues neural tube closure in cultured embryos. RhoA signalling is also overactivated, with accumulation of actomyosin in the Zic2Ku/Ku neuroepithelium, and the myosin inhibitor Blebbistatin partially normalises neural tube closure. However, dorsomorphin and Blebbistatin differ in their effects at tissue and cellular levels: DLHP formation is rescued by dorsomorphin but not Blebbistatin, whereas abnormal accumulation of actomyosin is rescued by Blebbistatin but not dorsomorphin. These findings suggest a dual mechanism of spina bifida origin in Zic2Ku/Ku embryos: faulty BMP-dependent formation of DLHPs and RhoA-dependent F-actin accumulation in the neuroepithelium. Hence, we identify a multi-pathway origin of spina bifida in a mammalian system that may provide a developmental basis for understanding the corresponding multifactorial human defects.

Indexed as

Neural Tube DefectsSpinal DysraphismActomyosinAnimalsHumansMammalsMiceNeural TubeNeurulationNuclear ProteinsTranscription FactorsActomyosinNuclear ProteinsTranscription FactorsZIC2 protein, humanActomyosinBMPEmbryoMorphogenesisNeural tube defectsNeurulation

Identifiers

PMID36916392
PMCPMC10073009
OpenAlexW4321749205

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.