Evidence map›Paper›PMID 29290584›Full record

ArticleDevelopmental cell2018

CRISPR Screens Uncover Genes that Regulate Target Cell Sensitivity to the Morphogen Sonic Hedgehog.

Ganesh V Pusapati, Jennifer H Kong, Bhaven B Patel, Arunkumar Krishnan, Andreas Sagner, Maia Kinnebrew, James Briscoe, L Aravind, Rajat Rohatgi

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

75 citing papers in PubMed, 135 citations in OpenAlex.

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  13. "Design principles of a membrane-spanning ubiquitin ligase".bioRxiv : the preprint server for biology · 2025
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Ganesh V PusapatiDepartments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: ganesh22@stanford.edu.
Jennifer H KongDepartments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bhaven B PatelDepartments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Arunkumar KrishnanNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Andreas SagnerThe Francis Crick Institute, Midland Road, London NW1 1AT, UK.
Maia KinnebrewDepartments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
James BriscoeThe Francis Crick Institute, Midland Road, London NW1 1AT, UK.
L AravindNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Rajat RohatgiDepartments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: rrohatgi@stanford.edu.
Stanford University · USThe Francis Crick Institute · GBNational Center for Biotechnology Information · USNational Institutes of Health · US

Funding

Evolutionary Analysis and Comparative Genomics of Protein SuperfamiliesZIALM594244 · NLM · NATIONAL LIBRARY OF MEDICINE · PI ARAVIND, L · 2009 to 2025
$20.3M
Supplement application for an Olympus automated microscopeR35GM118082 · NIGMS · STANFORD UNIVERSITY · PI RAJAT ROHATGI · 2016 to 2026
$7.6M
Reconstructing Primary CiliaDP2GM105448 · NIGMS · STANFORD UNIVERSITY · PI ROHATGI, RAJAT · 2012 to 2012
$2.4M
Molecular dissection of signal transduction at primary ciliaR01GM112988 · NIGMS · STANFORD UNIVERSITY · PI ROHATGI, RAJAT · 2015 to 2016
$618k
Cancer Research UK FC001051Medical Research CouncilNIGMS NIH HHS DP2 GM105448NIGMS NIH HHS R01 GM112988NIGMS NIH HHS R35 GM118082Wellcome TrustWellcome Trust WT098326MA
6 · The paper itself

Abstract

To uncover regulatory mechanisms in Hedgehog (Hh) signaling, we conducted genome-wide screens to identify positive and negative pathway components and validated top hits using multiple signaling and differentiation assays in two different cell types. Most positive regulators identified in our screens, including Rab34, Pdcl, and Tubd1, were involved in ciliary functions, confirming the central role for primary cilia in Hh signaling. Negative regulators identified included Megf8, Mgrn1, and an unannotated gene encoding a tetraspan protein we named Atthog. The function of these negative regulators converged on Smoothened (SMO), an oncoprotein that transduces the Hh signal across the membrane. In the absence of Atthog, SMO was stabilized at the cell surface and concentrated in the ciliary membrane, boosting cell sensitivity to the ligand Sonic Hedgehog (SHH) and consequently altering SHH-guided neural cell-fate decisions. Thus, we uncovered genes that modify the interpretation of morphogen signals by regulating protein-trafficking events in target cells.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsAnimalsCell MovementCiliaFluorescenceHedgehog ProteinsMembrane ProteinsMiceNeuronsNIH 3T3 CellsSignal TransductionSmoothened ReceptorHedgehog ProteinsMembrane ProteinsSmoothened ReceptorSmo protein, mouseciliopathycongenital heart diseaseCRISPR screenHedgehog signalingheterotaxymorphogen signalingneural tube patterningprimary ciliaprotein traffickingSmoothened

Identifiers

PMID29290584
PMCPMC5792066
OpenAlexW2775965165

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.