Evidence map›Paper›PMID 27552050›Full record

ArticleeLife2016

Patched1 and Patched2 inhibit Smoothened non-cell autonomously.

Brock Roberts, Catalina Casillas, Astrid C Alfaro, Carina Jägers, Henk Roelink

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
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  9. Article
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  14. Article
  15. Patched-2 functions to limit Patched-1 deficient skin cancer growth.Cellular oncology (Dordrecht, Netherlands) · 2018
    Article
  16. Skin-Derived Vitamin DThe Journal of investigative dermatology · 2017
    Article
  17. Review
  18. Review
  19. Review
  20. Review
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

5 authors at 1 institution in 1 country.

Brock RobertsDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Catalina CasillasDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Astrid C AlfaroDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Carina JägersDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Henk RoelinkDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.ORCID 0000-0002-5260-3634
California Institute of Technology · US

Funding

Sonic Hedgehog is a Calcium-regulated Zinc peptidaseR01GM117090 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROELINK, HENK · 2016 to 2022
$1.9M
The roles of Ptch1 and Disp1 in the formation of the Shh gradientR01GM097035 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROELINK, HENK · 2011 to 2014
$1.2M
NIGMS NIH HHS R01 GM097035NIGMS NIH HHS R01 GM117090
6 · The paper itself

Abstract

Smoothened (Smo) inhibition by Patched (Ptch) is central to Hedgehog (Hh) signaling. Ptch, a proton driven antiporter, is required for Smo inhibition via an unknown mechanism. Hh ligand binding to Ptch reverses this inhibition and activated Smo initiates the Hh response. To determine whether Ptch inhibits Smo strictly in the same cell or also mediates non-cell-autonomous Smo inhibition, we generated genetically mosaic neuralized embryoid bodies (nEBs) from mouse embryonic stem cells (mESCs). These experiments utilized novel mESC lines in which Ptch1, Ptch2, Smo, Shh and 7dhcr were inactivated via gene editing in multiple combinations, allowing us to measure non-cell autonomous interactions between cells with differing Ptch1/2 status. In several independent assays, the Hh response was repressed by Ptch1/2 in nearby cells. When 7dhcr was targeted, cells displayed elevated non-cell autonomous inhibition. These findings support a model in which Ptch1/2 mediate secretion of a Smo-inhibitory cholesterol precursor.

Indexed as

AnimalsGene Knockout TechniquesHedgehog ProteinsMiceMouse Embryonic Stem CellsPatched-1 ReceptorPatched-2 ReceptorSignal TransductionSmoothened ReceptorHedgehog ProteinsPatched-1 ReceptorPatched-2 ReceptorPtch1 protein, mousePtch2 protein, mouseSmoothened ReceptorSmo protein, mousedevelopmental biologymousepatchedRND antiportersShhSmostem cells

Identifiers

PMID27552050
PMCPMC5014547
OpenAlexW2513566282

What OpenQuestion holds

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LicenceCC BY
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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.