Evidence map›Paper›PMID 34496254›Full record

ArticleCell reports2021

Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons.

Yung-Chih Cheng, Andrew Snavely, Lee B Barrett, Xuefei Zhang, Crystal Herman, Devlin J Frost, Priscilla Riva, Ivan Tochitsky, Riki Kawaguchi, Bhagat Singh and 17 more

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

Article in Cell reports, 2021. 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
1.5field-weighted citation impact, top 17% 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, 28 citations in OpenAlex.

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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

27 authors at 3 institutions in 1 country.

Yung-Chih ChengF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Andrew SnavelyF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Lee B BarrettF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Xuefei ZhangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Crystal HermanF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Devlin J FrostF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Priscilla RivaF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Ivan TochitskyF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Riki KawaguchiDepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Bhagat SinghF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Jelena IvanisF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Eric A HuebnerF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Anthony ArvanitesHarvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Vatsal OzaHarvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Lance DavidowHarvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Rie MaedaF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Miyuki SakumaF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Alyssa GranthamF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Qing WangDepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Amelia N ChangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Kathleen PfaffHarvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Michael CostiganF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Anaesthesia Department, Boston Children's Hospital, Boston, MA 02115, USA.
Giovanni CoppolaDepartments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Lee L RubinDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Bjoern SchwerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Frederick W AltProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Clifford J WoolfF.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: clifford.woolf@childrens.harvard.edu.
Boston Children's Hospital · USHarvard Stem Cell Institute · USHarvard University · US

Funding

Unravelling Mechanisms and Novel Therapeutic Targets for Peripheral Neuropathy and Neuropathic Pain (Diversity Supplement)R35NS105076 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WOOLF, CLIFFORD J · 2018 to 2025
$9.5M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI WOOLF, CLIFFORD J · 2016 to 2020
$5.2M
NICHD NIH HHS P50 HD105351NICHD NIH HHS U54 HD090255NINDS NIH HHS R35 NS105076
6 · The paper itself

Abstract

Although axonal damage induces rapid changes in gene expression in primary sensory neurons, it remains unclear how this process is initiated. The transcription factor ATF3, one of the earliest genes responding to nerve injury, regulates expression of downstream genes that enable axon regeneration. By exploiting ATF3 reporter systems, we identify topoisomerase inhibitors as ATF3 inducers, including camptothecin. Camptothecin increases ATF3 expression and promotes neurite outgrowth in sensory neurons in vitro and enhances axonal regeneration after sciatic nerve crush in vivo. Given the action of topoisomerases in producing DNA breaks, we determine that they do occur immediately after nerve damage at the ATF3 gene locus in injured sensory neurons and are further increased after camptothecin exposure. Formation of DNA breaks in injured sensory neurons and enhancement of it pharmacologically may contribute to the initiation of those transcriptional changes required for peripheral nerve regeneration.

Indexed as

Activating Transcription Factor 3AnimalsAxonsDNA BreaksDNA Topoisomerases, Type IGene ExpressionMiceMice, Inbred C57BLNerve RegenerationNeuronal OutgrowthPeripheral Nerve InjuriesSciatic NerveSensory Receptor CellsActivating Transcription Factor 3Atf3 protein, mouseDNA Topoisomerases, Type IATF3DNA breaksneuronregenerationtopoisomerase

Identifiers

PMID34496254
PMCPMC8462619
OpenAlexW3196752787

What OpenQuestion holds

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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.