Evidence map›Paper›PMID 42642386›Full record

ArticleNature communications2026

Receptor allostery promotes context-specific Sonic Hedgehog signaling during embryonic development.

Miriam E Dillard, Christina A Daly, Rojalin Pradhan, Shariq S Ansari, Samantha J Hack, William C Wright, Daniel P Stewart, Mohamed A Ghonim, Yan Zhang, Robin Canac and 11 more

Abstract read
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

5 · Who and what money

Authors and funding

21 authors.

Miriam E Dillard *Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Christina A Daly *Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-7470-0454
Rojalin PradhanDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Shariq S AnsariDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Samantha J HackDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-3638-4750
William C WrightDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-2274-9966
Daniel P StewartDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Mohamed A GhonimDepartment of Host Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
Yan ZhangDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Robin CanacDepartment of Pediatrics, The University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-9036-1496
Ivan P MoskowitzDepartment of Pediatrics, The University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-0014-4963
Shondra M Pruett-MillerDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0002-3793-585X
Jeffrey SteinbergCenter for In Vivo Imaging and Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0003-4110-3586
Yong-Dong WangDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-8751-9216
April D SykesDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Motomi MoriDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Christopher C HomDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Taosheng ChenDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-6420-3809
Paul G ThomasDepartment of Host Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID http://orcid.org/0000-0001-7955-0256
James P BridgesDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA.ORCID http://orcid.org/0000-0002-4815-117X
Stacey K OgdenDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. Stacey.Ogden@stjude.org.ORCID http://orcid.org/0000-0001-8991-3065

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Mechanisms of Sonic Hedgehog Signal TransductionR35GM122546 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Stacey Kathryn Ogden · 2017 to 2026
$4.8M
NCI NIH HHS P30 CA021765NIGMS NIH HHS R35 GM122546U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30CA021765U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM122546
6 · The paper itself

Abstract

Sonic Hedgehog (SHH) signaling functions in temporal- and context-dependent manners to pattern diverse tissues during embryogenesis. The signal transducer Smoothened (SMO) is induced by sterols, oxysterols, and arachidonic acid (AA) through binding pockets in its extracellular cysteine-rich domain (CRD) and 7-transmembrane (7TM) bundle. In vitro analyses suggest SMO signaling is allosterically enhanced by combinatorial ligand binding to these pockets, but in vivo evidence of SMO allostery is lacking. Herein, we map an AA binding pocket at the top of the 7TM bundle and show that its disruption attenuates SHH- and sterol-stimulated SMO induction. A knock-in mouse model of compromised AA binding reveals that homozygous mutant mice are cyanotic, exhibit perinatal lethality, and display congenital heart disease. Surviving mutants demonstrate pulmonary maldevelopment and fail to thrive. Neurodevelopment is unaltered in these mice, suggesting that context-specific allosteric regulation of SMO signaling allows for precise tuning of pathway activity during cardiopulmonary development.

Indexed as

Embryonic DevelopmentHedgehog ProteinsSignal TransductionSmoothened ReceptorAllosteric RegulationAnimalsArachidonic AcidBinding SitesFemaleGene Knock-In TechniquesHumansMiceArachidonic AcidHedgehog ProteinsShh protein, mouseSmoothened ReceptorSmo protein, mouse

Identifiers

PMID42642386
PMCPMC13507325

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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.