Evidence map›Paper›PMID 41571667›Full record

ArticleNature communications2026

Neural crest cell-derived DKK1 and NEDD4 modulate Wnt signalling in the second heart field to orchestrate outflow tract development.

Sophie Wiszniak, Dimuthu Alankarage, Iman Lohraseb, Ceilidh Marchant, Genevieve Secker, Deepti Domingo, Jasmine Hartmann, Tianyang Zhang, Wendy Parker, John Toubia and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Sophie WiszniakCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. Sophie.wiszniak@adelaide.edu.au.ORCID http://orcid.org/0000-0001-8666-9300
Dimuthu AlankarageVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Iman LohrasebCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
Ceilidh MarchantCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
Genevieve SeckerCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
Deepti DomingoCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
Jasmine HartmannCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
Tianyang ZhangCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.ORCID http://orcid.org/0009-0006-7243-8812
Wendy ParkerCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
John ToubiaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-5135-6504
Melissa WhiteSchool of Biomedicine and Robinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
Sandra PiltzSchool of Biomedicine and Robinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0003-3386-8140
Markus TondlCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.
Eleni GiannoulatouVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.ORCID http://orcid.org/0000-0002-7084-6736
David WinlawHeart Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-8005-3361
Gillian M BlueHeart Centre for Children, The Children's Hospital at Westmead, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-1480-9535
Congenital Heart Disease Synergy Group
Patrick P L TamChildren's Medical Research Institute, University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0001-6950-8388
Paul ThomasSchool of Biomedicine and Robinson Research Institute, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-5002-5770
Natasha HarveyCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0001-9839-8966
Sally L DunwoodieVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.ORCID http://orcid.org/0000-0002-2069-7349
Quenten SchwarzCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia. Quenten.schwarz@adelaide.edu.au.ORCID http://orcid.org/0000-0002-5958-4181

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cardiac outflow tract morphogenesis requires coordinated interactions between multiple cell populations and is dependent on the contribution of cardiac progenitors from the second heart field. While neural crest cells have been proposed to impact second heart field development, how they regulate progenitor behaviour remains unclear. Here, we discover neural crest cells are a primary source of Dickkopf-1 (DKK1) which modulates Wnt signalling activity in the second heart field to influence the balance between cardiac progenitor maintenance and differentiation. We show that the ubiquitin ligase NEDD4 regulates DKK1, with disruption of Nedd4 leading to outflow tract defects. We further identify a new NEDD4 variant underlying human congenital heart disease. Our findings uncover an unexpected role for neural crest cells as a rheostat of Wnt signalling in cardiac progenitors, identifying a new molecular pathway promoting outflow tract morphogenesis, and a new causative factor of congenital heart disease.

Indexed as

HeartIntercellular Signaling Peptides and ProteinsNedd4 Ubiquitin Protein LigasesNeural CrestWnt Signaling PathwayAnimalsCell DifferentiationGene Expression Regulation, DevelopmentalHeart Defects, CongenitalHumansMiceDKK1 protein, humanDkk1 protein, mouseIntercellular Signaling Peptides and ProteinsNedd4 protein, humanNedd4 protein, mouseNedd4 Ubiquitin Protein Ligases

Identifiers

PMID41571667
PMCPMC12913648

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.