The Ras/Raf/ERK signalling pathway drives Schwann cell dedifferentiation

The EMBO Journal
Marie C HarrisinghAlison C Lloyd

Abstract

Schwann cells are a regenerative cell type. Following nerve injury, a differentiated myelinating Schwann cell can dedifferentiate and regain the potential to proliferate. These cells then redifferentiate during the repair process. This behaviour is important for successful axonal repair, but the signalling pathways mediating the switch between the two differentiation states remain unclear. Sustained activation of the Ras/Raf/ERK cascade in primary cells results in a cell cycle arrest and has been implicated in the differentiation of certain cell types, in many cases acting to promote differentiation. We therefore investigated its effects on the differentiation state of Schwann cells. Surprisingly, we found that Ras/Raf/ERK signalling drives the dedifferentiation of Schwann cells even in the presence of normal axonal signalling. Furthermore, nerve wounding in vivo results in sustained ERK signalling in associated Schwann cells. Elevated Ras signalling is thought to be important in the development of Schwann cell-derived tumours in neurofibromatosis type 1 patients. Our results suggest that the effects of Ras signalling on the differentiation state of Schwann cells may be important in the pathogenesis of these tumours.

References

Jul 1, 1990·Journal of Neuroscience Research·A C LeBlanc, J F Poduslo
Dec 1, 1989·Neuron·E S MonukiG Lemke
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·B R SevetsonJ C Lawrence
Nov 12, 1993·Science·S J Cook, F McCormick
May 1, 1995·The Journal of Cell Biology·L ChengA W Mudge
Feb 1, 1996·Current Opinion in Neurobiology·R Mirsky, K R Jessen
Mar 1, 1997·Genes & Development·A C LloydH Land
Sep 8, 1998·Current Opinion in Genetics & Development·M Freeman
Nov 24, 1998·Trends in Genetics : TIG·P W Sternberg, M Han
Dec 10, 1999·Annals of the New York Academy of Sciences·T RosenbaumN Ratner
Nov 1, 2000·Cell·D Bar-Sagi, A Hall
Nov 25, 2000·Cellular and Molecular Life Sciences : CMLS·P Crespo, J León
Feb 7, 2001·Science·N F MathonA C Lloyd
Mar 10, 2001·Cell·K Cichowski, T Jacks
Mar 21, 2001·The Journal of Cell Biology·G ZanazziJ L Salzer
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Mar 18, 2003·Molecular and Cellular Biology·Philip J MitchellAlison C Lloyd
Oct 1, 1999·Annals of the New York Academy of Sciences·Thorsten RosenbaumNancy Ratner

❮ Previous
Next ❯

Citations

Jul 25, 2007·Cellular and Molecular Neurobiology·Ai-Guo ShenChun Cheng
Sep 8, 2012·Journal of Clinical Immunology·André HeinenPatrick Küry
Nov 13, 2007·Journal of Molecular Neuroscience : MN·Jeffery D HainesGuillermina Almazan
Oct 19, 2006·Nature Reviews. Genetics·Alejandro Sánchez Alvarado, Panagiotis A Tsonis
Feb 16, 2013·Brain : a Journal of Neurology·Robin D S DoddrellDavid B Parkinson
Jun 19, 2008·Genes & Development·Karim NadraRoman Chrast
Dec 6, 2008·Genes & Development·Simona ParrinelloAlison C Lloyd
May 19, 2011·Development, Growth & Differentiation·Emily Roberge-White, Mariko Katoh-Kurasawa
Aug 14, 2012·Pharmacological Reviews·Kevin L FarmerRick T Dobrowsky
Nov 10, 2005·Science's STKE : Signal Transduction Knowledge Environment·Luke A Noon, Alison C Lloyd
May 6, 2009·Molecular and Cellular Biology·Vidya BodempudiFaris Farassati
Jun 29, 2013·The European Physical Journal. E, Soft Matter·Mao-Xiang WangC K Chan
Jan 30, 2010·Journal of Vascular Research·Kunju SathishkumarChandra Yallampalli
Aug 2, 2006·Journal of Biology·Alison C Lloyd
Apr 30, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Neeraja SyedHaesun A Kim
Aug 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Li-Jin ChewVittorio Gallo
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Akihiro IshiiRashmi Bansal
Feb 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Junyang JungHwan Tae Park
May 25, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David P YangHaesun A Kim
Jun 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shuibing ChenPeter G Schultz
Jun 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Nikos Tapinos, Anura Rambukkana
Mar 20, 2014·ASN Neuro·Daniela SchmidNicole Schaeren-Wiemers
Jul 14, 2010·Journal of Biomedicine & Biotechnology·Toshihiro Masaki, Kiichiro Matsumura
Sep 10, 2014·Nature Medicine·Rudolf Martini
May 8, 2014·Journal of Materials Science. Materials in Medicine·Antos ShakhbazauRajiv Midha
Aug 6, 2014·The Journal of Cell Biology·Mikael SimonsMartin Kerschensteiner
Oct 19, 2014·Neural Development·Maria Laura CeciMiguel L Allende
Aug 19, 2007·Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery·Kazuya KataokaLars B Dahlin
Jul 8, 2015·The Journal of Cell Biology·Michael Thumm, Mikael Simons
May 21, 2008·The Journal of Cell Biology·James L Salzer
May 21, 2008·The Journal of Cell Biology·David B ParkinsonKristján R Jessen
Feb 11, 2016·Cell Communication and Signaling : CCS·Anne HennigIgnacio Rubio
Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Elisa DuregottiMichela Rigoni

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.