Evidence map›Paper›PMID 29722913›Full record

ArticleGlia2018

The TSC1-mTOR-PLK axis regulates the homeostatic switch from Schwann cell proliferation to myelination in a stage-specific manner.

Minqing Jiang, Rohit Rao, Jincheng Wang, Jiajia Wang, Lingli Xu, Lai Man Wu, Jonah R Chan, Huimin Wang, Q Richard Lu

Abstract read
In one paragraph

Article in Glia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

7 citing papers in PubMed, 11 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

9 authors at 3 institutions in 2 countries.

Minqing JiangDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Rohit RaoDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Jincheng WangDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Jiajia WangDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Lingli XuDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Lai Man WuDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Jonah R ChanDepartment of Neurology and Programs in Biomedical and Neurosciences, University of California, San Francisco, California.
Huimin WangThe Institute of Cognitive Neuroscience, East China Normal University, Shanghai, China.
Q Richard LuDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.ORCID 0000-0001-6846-9014
Cincinnati Children's Hospital Medical Center · USEast China Normal University · CNUniversity of California, San Francisco · US

Funding

Medical Scientist Training ProgramT32GM063483 · NIGMS · UNIVERSITY OF CINCINNATI · PI KHURANA HERSHEY, GURJIT K. · 2002 to 2022
$6.7M
Molecular Mechanisms of Oligodendrocyte Differentiation and MyelinationR01NS072427 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI LU, QING R · 2010 to 2018
$3.6M
THE ESTABLISHMENT OF SCHWANN CELL POLARITY AND THE INITIATION OF MYELINATIONR01NS062796 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHAN, JONAH R · 2008 to 2018
$3.4M
Chromatin remodeling control of myelination and remyelinationR01NS075243 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI LU, QING R · 2012 to 2018
$2.6M
A Novel Model of Medulloblastoma to Define Cancer Pathways and Molecular TargetsR01NS078092 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI LU, QING R · 2012 to 2016
$1.7M
Molecular and signaling mechanisms of peripheral nerve sheath tumorigenesisR37NS096359 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI LU, QING R · 2016 to 2018
$1.6M
National Multiple Sclerosis Society NMSS-4727National Multiple Sclerosis Society R01NS062796National Natural Science Foundation of China NSFC 31271134NIGMS NIH HHS T32 GM063483NINDS NIH HHS R01 NS062796NINDS NIH HHS R01 NS072427NINDS NIH HHS R01 NS075243NINDS NIH HHS R01 NS078092NINDS NIH HHS R37 NS096359US National Institutes of Health R01NS072427US National Institutes of Health R01NS075243
6 · The paper itself

Abstract

Proper peripheral myelination depends upon the balance between Schwann cell proliferation and differentiation programs. The serine/threonine kinase mTOR integrates various environmental cues to serve as a central regulator of cell growth, metabolism, and function. We report here that tuberous sclerosis complex 1 (TSC1), a negative regulator of mTOR activity, establishes a stage-dependent program for Schwann cell lineage progression and myelination by controlling cell proliferation and myelin homeostasis. Tsc1 ablation in Schwann cell progenitors in mice resulted in activation of mTOR signaling, and caused over-proliferation of Schwann cells and blocked their differentiation, leading to hypomyelination. Transcriptome profiling analysis revealed that mTOR activation in Tsc1 mutants resulted in upregulation of a polo-like kinase (PLK)-dependent pathway and cell cycle regulators. Attenuation of mTOR or pharmacological inhibition of polo-like kinases partially rescued hypomyelination caused by Tsc1 loss in the developing peripheral nerves. In contrast, deletion of Tsc1 in mature Schwann cells led to redundant and overgrown myelin sheaths in adult mice. Together, our findings indicate stage-specific functions for the TSC1-mTOR-PLK signaling axis in controlling the transition from proliferation to differentiation and myelin homeostasis during Schwann cell development.

Indexed as

AnimalsCell CycleCell Cycle ProteinsCell ProliferationFemaleHomeostasisMaleMice, 129 StrainMice, Inbred C57BLMice, TransgenicNeural Stem CellsPolo-Like Kinase 1Protein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesBI 2536Cell Cycle ProteinsmTOR protein, mousePolo-Like Kinase 1Protein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesTOR Serine-Threonine KinasesTsc1 protein, mouseTuberous Sclerosis Complex 1 ProteinmTOR signalingmyelinationpolo-like kinaseproliferationSchwann cellTSCtumor suppressor

Identifiers

PMID29722913
PMCPMC6185760
OpenAlexW2799531253

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.