Evidence map›Paper›PMID 36495293›Full record

ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2023

Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.

Matthew T McLaughlin, Miranda R Sun, Tyler G Beames, Austin C Steward, Joshua W M Theisen, Hannah M Chung, Joshua L Everson, Ivan P Moskowitz, Michael D Sheets, Robert J Lipinski

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

Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2023. 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
0.2field-weighted citation impact, top 37% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  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

10 authors at 2 institutions in 1 country.

Matthew T McLaughlinDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Miranda R SunDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Tyler G BeamesDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Austin C StewardDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Joshua W M TheisenDepartment of Pediatrics, Pathology, Human Genetics, and Genetic Medicine, The University of Chicago, Chicago, Illinois, USA.
Hannah M ChungDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Joshua L EversonDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ivan P MoskowitzDepartment of Pediatrics, Pathology, Human Genetics, and Genetic Medicine, The University of Chicago, Chicago, Illinois, USA.
Michael D SheetsDepartment of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Robert J LipinskiDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0002-1994-4090
University of Wisconsin–Madison · USUniversity of Chicago · US

Funding

MULTIDISCIPLINARY CARDIAC SCIENCEST32HL007381 · NHLBI · UNIVERSITY OF CHICAGO · PI JEANNE M DECARA, Yoav Gilad · 1985 to 2026
$12.5M
Molecular & Environmental Toxicology Pre-& Postdoctoral Training ProgramT32ES007015 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI CHRISTOPHER A BRADFIELD · 1985 to 2026
$11.5M
Regulation of cell fates by the Bicaudal-C translational repressorR01HD091921 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI SHEETS, MICHAEL D · 2018 to 2022
$1.5M
Imaging and mechanistic analyses of face-brain dysmorphology in a CLP modelR00DE022101 · NIDCR · UNIVERSITY OF WISCONSIN-MADISON · PI LIPINSKI, ROBERT · 2013 to 2015
$725k
DNA Methylation in Orofacial CleftingR03DE027162 · NIDCR · UNIVERSITY OF WISCONSIN-MADISON · PI LIPINSKI, ROBERT · 2017 to 2018
$296k
NHLBI NIH HHS T32 HL007381NICHD NIH HHS R01 HD091921NIDCR NIH HHS R00 DE022101NIDCR NIH HHS R03 DE027162NIEHS NIH HHS T32 ES007015
6 · The paper itself

Abstract

backgroundFrem1 has been linked to human face shape variation, dysmorphology, and malformation, but little is known about its regulation and biological role in facial development.

resultsDuring midfacial morphogenesis in mice, we observed Frem1 expression in the embryonic growth centers that form the median upper lip, nose, and palate. Expansive spatial gradients of Frem1 expression in the cranial neural crest cell (cNCC) mesenchyme of these tissues suggested transcriptional regulation by a secreted morphogen. Accordingly, Frem1 expression paralleled that of the conserved Sonic Hedgehog (Shh) target gene Gli1 in the cNCC mesenchyme. Suggesting direct transcriptional regulation by Shh signaling, we found that Frem1 expression is induced by SHH ligand stimulation or downstream pathway activation in cNCCs and observed GLI transcription factor binding at the Frem1 transcriptional start site during midfacial morphogenesis. Finally, we found that FREM1 is sufficient to induce cNCC proliferation in a concentration-dependent manner and that Shh pathway antagonism reduces Frem1 expression during pathogenesis of midfacial hypoplasia.

conclusionsBy demonstrating that the Shh signaling pathway regulates Frem1 expression in cNCCs, these findings provide novel insight into the mechanisms underlying variation in midfacial morphogenesis.

Indexed as

Hedgehog ProteinsNeural CrestAnimalsExtracellular Matrix ProteinsHumansMesodermMiceMorphogenesisNitrosourea CompoundsSignal TransductionExtracellular Matrix ProteinsFrem1 protein, mouseHedgehog ProteinsNitrosourea CompoundsN,N'-bis((2-chloroethyl)nitrosocarbamoyl)cystaminefacial dysmorphologyfacial morphogenesisFrem/Frasmedial nasal processesmidface hypoplasia

Identifiers

PMID36495293
PMCPMC10066825
OpenAlexW4311931159

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.