Evidence map›Paper›PMID 40268889›Full record

ArticleNature communications2025

Nkx2.7 is a conserved regulator of craniofacial development.

Caitlin Ford, Carmen de Sena-Tomás, Tint Tha Ra Wun, Angelika G Aleman, Uday Rangaswamy, Jake Leyhr, María I Nuñez, Cynthia Zehui Gao, Hieu T Nim, Michael See and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

17 authors.

Caitlin FordDepartment of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.
Carmen de Sena-TomásDivision of Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-0477-6135
Tint Tha Ra WunDivision of Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.ORCID http://orcid.org/0009-0003-3150-3890
Angelika G AlemanDivision of Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.
Uday RangaswamyFunctional and Structural Genomics, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Via Bonomea 265, 34136, Trieste, Italy.ORCID http://orcid.org/0009-0007-2758-9213
Jake LeyhrDepartment of Organismal Biology, Uppsala University, 75236, Uppsala, Sweden.ORCID http://orcid.org/0000-0003-1815-7818
María I NuñezDivision of Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.ORCID http://orcid.org/0009-0005-9043-1828
Cynthia Zehui GaoDivision of Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.
Hieu T NimThe Novo Nordisk Foundation Center for Stem Cell Medicine & Stem Cell Biology, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0001-9320-0236
Michael SeeThe Novo Nordisk Foundation Center for Stem Cell Medicine & Stem Cell Biology, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0002-7231-3896
Ugo CoppolaMolecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Joshua S WaxmanMolecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-8132-487X
Mirana RamialisonThe Novo Nordisk Foundation Center for Stem Cell Medicine & Stem Cell Biology, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0001-6315-4777
Tatjana HaitinaDepartment of Organismal Biology, Uppsala University, 75236, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-8754-5534
Joanna SmeetonDepartment of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-6126-2560
Remo SangesFunctional and Structural Genomics, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Via Bonomea 265, 34136, Trieste, Italy.ORCID http://orcid.org/0000-0002-5047-9713
Kimara L TargoffDivision of Cardiology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA. kl284@columbia.edu.ORCID http://orcid.org/0000-0002-6066-6002

Funding

Molecular Mechanisms of Atrial Development and RegenerationR01HL137766 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Joshua Waxman · 2017 to 2026
$3.9M
Mechanisms governing the differentiation and maintenance of atrial identityR01HL168790 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Joshua Waxman · 2023 to 2026
$2.5M
Mechanisms of outflow tract morphogenesis regulated by extracellular matrixR01HL170188 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KIMARA L TARGOFF · 2023 to 2026
$2.1M
Mechanisms of myocardial regeneration mediated by Nkx2.5 in zebrafishR01HL162989 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KIMARA L TARGOFF · 2023 to 2026
$2.0M
Cardiac Transcription Factor Nkx2.7 is a Novel Regulator of Craniofacial DevelopmentF31DE030385 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FORD, CAITLIN KELLY · 2021 to 2022
$94k
Essential functions of Fibulin proteins in outflow tract morphogenesis.F31HL164101 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALEMAN, ANGELIKA G. · 2022 to 2023
$88k
NHLBI NIH HHS F31 HL164101NHLBI NIH HHS R01 HL137766NHLBI NIH HHS R01 HL162989NHLBI NIH HHS R01 HL168790NHLBI NIH HHS R01 HL170188NIDCR NIH HHS F31 DE030385U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 HL13143801A1
6 · The paper itself

Abstract

Craniofacial malformations arise from developmental defects in the head, face, and neck with phenotypes such as 22q11.2 deletion syndrome illustrating a developmental link between cardiovascular and craniofacial morphogenesis. NKX2-5 is a key cardiac transcription factor associated with congenital heart disease and mouse models of Nkx2-5 deficiency highlight roles in cardiac development. In zebrafish, nkx2.5 and nkx2.7 are paralogues in the NK4 family expressed in cardiomyocytes and pharyngeal arches. Despite shared cellular origins of cardiac and craniofacial tissues, the function of NK4 factors in head and neck patterning has not been elucidated. Molecular evolutionary analysis of NK4 genes shows that nkx2.5 and nkx2.7 are ohnologs resulting from whole genome duplication events. Nkx2.7 serves as a previously unappreciated regulator of branchiomeric muscle and cartilage formation for which nkx2.5 cannot fully compensate. Mechanistically, our results highlight that Nkx2.7 patterns the cranial neural crest and functions upstream of Endothelin1 to inhibit Notch signals. Together, our studies shed light on an evolutionarily conserved Nkx transcription factor with unique functions in vertebrate craniofacial development, advancing our understanding of congenital head and neck deformities.

Indexed as

Homeodomain ProteinsSkullTranscription FactorsZebrafish ProteinsAnimalsBranchial RegionCraniofacial AbnormalitiesEndothelin-1Evolution, MolecularGene Expression Regulation, DevelopmentalHomeobox Protein Nkx-2.5MiceNeural CrestReceptors, NotchSignal TransductionZebrafishEndothelin-1Homeobox Protein Nkx-2.5Homeodomain ProteinsNkx2.5 protein, zebrafishReceptors, NotchTranscription FactorsZebrafish Proteins

Identifiers

PMID40268889
PMCPMC12019251

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.