Evidence map›Paper›PMID 40891441›Full record

ArticleDevelopment (Cambridge, England)2025

The non-canonical thioreductase Tmx2b is essential for neuronal survival during zebrafish embryonic brain development.

Jordy Dekker, Wendy Lam, Herma C van der Linde, Floris Ophorst, Charlotte de Konink, Rachel Schot, Gert-Jan Kremers, Leslie E Sanderson, Woutje M Berdowski, Geeske M van Woerden and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Jordy DekkerDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Wendy LamDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Herma C van der LindeDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Floris OphorstDepartment of Pathology, Optical Imaging Center, Erasmus MC University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
Charlotte de KoninkDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Rachel SchotDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Gert-Jan KremersDepartment of Pathology, Optical Imaging Center, Erasmus MC University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
Leslie E SandersonDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-8026-406X
Woutje M BerdowskiDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Geeske M van WoerdenDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0003-2492-9239
Grazia M S ManciniDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Tjakko J van HamDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-2175-8713

Funding

Erasmus Universiteit Rotterdam Erasmus University Rotterdam (EUR) fellowshipErasmus University Rotterdam
6 · The paper itself

Abstract

Biallelic variants in thioredoxin-related transmembrane 2 protein (TMX2) can cause a malformation of brain cortical development characterized by microcephaly, polymicrogyria and pachygyria by an unknown mechanism. To investigate and visualize how TMX2 loss disrupts brain development in vivo, we generated zebrafish deficient for TMX2 ortholog tmx2b, which during the first two developmental days showed normal brain developmental hallmarks. From 3 days onwards, however, tmx2b mutants had no locomotor activity; this was accompanied by cell death in the brain, but not in other organs or in the spinal cord. Strikingly, cell death in tmx2b mutants occurred specifically in post-mitotic neurons within a ∼1.5-h timeframe, whereas neuronal progenitor and radial glial cells were preserved, and could be suppressed by inhibiting neuronal activity. In vivo calcium imaging showed a persistent ∼2-fold increase in calcium in neurons after the onset of cell death. This suggests that calcium homeostasis underlies the tmx2b mutant brain phenotype. Our results indicate that TMX2 is an evolutionarily conserved, protective regulator essential specifically for post-mitotic neurons after their differentiation in the vertebrate embryonic brain.

Indexed as

BrainNeuronsZebrafishZebrafish ProteinsAnimalsCalciumCell DeathCell DifferentiationCell SurvivalEmbryo, NonmammalianGene Expression Regulation, DevelopmentalMutationNeurogenesisCalciumZebrafish ProteinsCortical developmentMicrocephalyPolymicrogyriaTMX2Zebrafish

Identifiers

PMID40891441
PMCPMC12516324

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.