TEAM

Stem cells and brain repair

Group leader : P. Durbec

Our team seeks to understand the repair process in the adult brain and more specifically the regeneration of the myelin sheath.

FOR BEGINNERS
Demyelination in the corpus callosum of an adult mouse brain by the Durbec Team from IBDM, IBDML

Demyelination in the corpus callosum of an adult mouse brain.

Myelin is a sheath that surrounds and insulates the nerve, and improves signal transmission. When myelin is damaged or abnormal, due to genetic abnormalities, trauma or neurodegenerative diseases such as multiple sclerosis, neurological disorders occur resulting in severe disability.

The nervous system is capable, to a certain extent, to regenerate the myelin sheath, but this self-repair process is incomplete and insufficient. This regeneration is possible thanks to the presence in the brain of stem cells and progenitor cells that can replace oligodendrocytes the myelin forming cell. It is therefore important to understand all the mechanisms involved in the process of myelin repair in order to develop new therapeutic strategies.

Oligodendrocyte progenitors migrating in culture by the Durbec Team from IBDM, IBDML

Oligodendrocyte progenitors migrating in culture.

Our research aims to better understand the biology of adult progenitor and stem cells involved in remyelination. Our goal is to decipher the cellular and molecular mechanisms controlling the mobilization of these cells. We are trying to determine which cells are involved in the repair process. How these cells migrate to the lesion site? What are the factors that control their differentiation into oligodendrocytes in physiological and pathological conditions? We are looking for factors that can influence or control these events when administered to the animal. We use the mouse as a model organism and combine techniques of cell biology, molecular imaging and neurosurgery to answer these questions.

FOR SPECIALISTS
Oligodendrocyte and neurons in co-culture by the Durbec Team from IBDM, IBDML

Oligodendrocyte (green) and neurons (red) in co-culture.

The team focuses on the process of post-lesional plasticity following demyelination in the adult brain. In some patients affected by multiple sclerosis (MS) spontaneous remyelination can occur. Although insufficient to counter the damages caused by the repetitive attacks, this spontaneous regenerative process represent great therapeutic hopes. Studies led on rodent have identified two distinct sources of cells involved in remyelination: the oligodendrocyte progenitors (OPCs) found throughout the brain parenchyma and neural progenitor derived from the sub-ventricular zone (SVZ) were adult neural stem cells reside. Our objectives are to uncover the cellular and molecular mechanisms controlling this process in order to increase our fundamental knowledge on brain regeneration and to promote the myelin repair.

Oligodendrocyte progenitor in culture by the Durbec Team from IBDM, IBDML

Oligodendrocyte progenitor in culture.

In our previous work, we showed that the proliferation, migration and differentiation of the OPCs and neural progenitors of the SVZ can be controlled to improve the process of cellular replacement. We identified factors that control the migration of the SVZ-derived progenitors and OPCs toward the demyelination lesions. We have shown that certain signals expressed in the lesion specifically regulate cell motility and detachment, as others are chemo-attractants.

More recently, we compared the gene expression of SVZ cells from healthy adult mice to mice with an experimental model of MS. We have identified factors whom expression is specifically regulated during the mobilization process after demyelination. We are currently focusing our attention on factors that promote angiogenesis and those that regulate the dialogue with the environment and the extracellular matrix.


Main publications

PUBLICATION

Region and dynamic specificities of adult neural stem cells and oligodendrocyte precursors in myelin regeneration in the mouse brain.

Brousse B, Magalon K, Durbec P, Cayre M.
Biol Open. 2015 Jul 3;4(8):980-92. PMID: 26142314

PUBLICATION

Oligodendrogenesis in the normal and pathological central nervous system.

El Waly B, Macchi M, Cayre M, Durbec P.
Front Neurosci. 2014 Jun 12;8:145. PMID: 24971048

PUBLICATION

Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero.

Salmi M, Bruneau N, Cillario J, Lozovaya N, Massacrier A, Buhler E, Cloarec R, Tsintsadze T, Watrin F, Tsintsadze V, Zimmer C, Villard C, Lafitte D, Cardoso C, Bao L, Lesca G, Rudolf G, Muscatelli F, Pauly V, Khalilov I, Durbec P, Ben-Ari Y, Burnashev N, Represa A, Szepetowski P.
Brain. 2013 Jul 5. PMID: 23831613

PUBLICATION

Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination.

Cayre M, Courtès S, Martineau F, Giordano M, Arnaud K, Zamaron A, Durbec P.
Development. 2013 Jul 3. PMID: 23824572

PUBLICATION

Ciliary Neurotrophic Factor Controls Progenitor Migration during Remyelination in the Adult Rodent Brain.

Vernerey J, Macchi M, Magalon K, Cayre M, Durbec P.
J Neurosci. 2013 Feb 13;33(7):3240-50. PMID: 23407977

PUBLICATION

Sonic Hedgehog Signaling Is a Positive Oligodendrocyte Regulator during Demyelination.

Ferent J, Zimmer C, Durbec P, Ruat M, Traiffort E.
J Neurosci. 2013 Jan 30;33(5):1759-72. PMID: 23365216

PUBLICATION

Olesoxime accelerates myelination and promotes repair in models of demyelination.

Magalon K, Zimmer C, Cayre M, Khaldi J, Bourbon C, Robles I, Tardif G, Viola A, Pruss RM, Bordet T, Durbec P.
Ann Neurol. 2012 Feb;71(2):213-26. PMID: 22367994

PUBLICATION

A lateral belt of cortical LGN and NuMA guides mitotic spindle movements and planar division in neuroepithelial cells.

Peyre E, Jaouen F, Saadaoui M, Haren L, Merdes A, Durbec P, Morin X.
J Cell Biol. 2011 Apr 4;193(1):141-54. PMID: 21444683

PUBLICATION

RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres.

Popa N, Cedile O, Pollet-Villard X, Bagnis C, Durbec P, Boucraut J.
Glia. 2011 Jan;59(1):35-44. PMID: 21046555

PUBLICATION

Reelin controls progenitor cell migration in the healthy and pathological adult mouse brain.

Courtès S, Vernerey J, Pujadas L, Magalon K, Cremer H, Soriano E, Durbec P, Cayre M.
PLoS One. 2011;6(5):e20430. PMID: 21647369

PUBLICATION

Cell migration in the normal and pathological postnatal mammalian brain

Cayre M, Canoll P, Goldman JE.
Prog Neurobiol. 2009 May;88(1):41-63. doi: 10.1016/j.pneurobio.2009.02.001. PMID: 19428961

PUBLICATION

Intranasal HB-EGF administration favors adult SVZ cell mobilization to demyelinated lesions in mouse corpus callosum.

Cantarella C, Cayre M, Magalon K, Durbec P.
Dev Neurobiol. 2008 Feb 1;68(2):223-36. PMID: 18000828

PUBLICATION

LIFR beta plays a major role in neuronal identity determination and glial differentiation in the mouse facial nucleus.

Alfonsi F, Filippi P, Salaun D, deLapeyrière O, Durbec P.
Dev Biol. 2008 Jan 1;313(1):267-78. PMID: 18031722

PUBLICATION

Characterization of heterogeneous glial cell populations involved in dehydration-induced proliferation in the adult rat neurohypophysis.

Virard I, Gubkina O, Alfonsi F, Durbec P.
Neuroscience. 2008 Jan 2;151(1):82-91. PMID: 18082334

PUBLICATION

In vitro migration assays of neural stem cells.

Durbec P, Franceschini I, Lazarini F, Dubois-Dalcq M.
Methods Mol Biol. 2008;438:213-25. PMID: 18369761

PUBLICATION

Control of planar divisions by the G-protein regulator LGN maintains progenitors in the chick neuroepithelium.

Morin X, Jaouen F, Durbec P.
Nat Neurosci. 2007 Nov;10(11):1440-8. PMID: 17934458

PUBLICATION

Relevance of combinatorial profiles of intermediate filaments and transcription factors for glioma histogenesis.

Colin C, Virard I, Baeza N, Tchoghandjian A, Fernandez C, Bouvier C, Calisti A, Tong S, Durbec P, Figarella-Branger D.
Neuropathol Appl Neurobiol. 2007 Aug;33(4):431-9. PMID: 17442061

PUBLICATION

PSA-NCAM in postnatally generated immature neurons of the olfactory bulb: a crucial role in regulating p75 expression and cell survival.

Gascon E, Vutskits L, Jenny B, Durbec P, Kiss JZ.
Development. 2007 Mar;134(6):1181-90. PMID: 17301083

PUBLICATION

Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models.

Magalon K, Cantarella C, Monti G, Cayre M, Durbec P.
Eur J Neurosci. 2007 Feb;25(3):761-71. PMID: 17298600

PUBLICATION

Migrating and myelinating potential of subventricular zone neural progenitor cells in white matter tracts of the adult rodent brain.

Cayre M, Bancila M, Virard I, Borges A, Durbec P.
Mol Cell Neurosci. 2006 Apr;31(4):748-58. PMID: 16481195

PUBLICATION

In vitro identification and functional characterization of glial precursor cells in human gliomas.

Colin C, Baeza N, Tong S, Bouvier C, Quilichini B, Durbec P, Figarella-Branger D.
Neuropathol Appl Neurobiol. 2006 Apr;32(2):189-202. PMID: 16599947

PUBLICATION

Oligodendrocyte precursor cells generate pituicytes in vivo during neurohypophysis development.

Virard I, Coquillat D, Bancila M, Kaing S, Durbec P.
Glia. 2006 Feb;53(3):294-303. PMID: 16265670

PUBLICATION

Migrating and myelinating potential of neural precursors engineered to overexpress PSA-NCAM.

Franceschini I, Vitry S, Padilla F, Casanova P, Tham TN, Fukuda M, Rougon G,Durbec P, Dubois-Dalcq M.
Mol Cell Neurosci. 2004 Oct;27(2):151-62. PMID: 15485771

PUBLICATION

Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity.

Torregrossa P, Buhl L, Bancila M, Durbec P, Schafer C, Schachner M, Rougon G.
J Biol Chem. 2004 Jul 16;279(29):30707-14. PMID: 15131117

PUBLICATION

A role for the polysialic acid-neural cell adhesion molecule in PDGF-induced chemotaxis of oligodendrocyte precursor cells.

Zhang H, Vutskits L, Calaora V, Durbec P, Kiss JZ.
J Cell Sci. 2004 Jan 1;117(Pt 1):93-103. PMID: 14627627
Other publications

Interactions

IBDM
NATIONAL
  • A. Viola
  • M. Ruat E. Traifford
  • F. Muscatelli
  • P. Szepetowski
  • T. Bordet Rebecca Pruss
INTERNATIONAL
  • K. Grobe
  • P. Brundin
  • E. Angot

Lab Twitter


Funding

ANR funding for P. Durbec Team from IBDM, IBDML

ARSEP funding for P. Durbec Team from IBDM, IBDML

FRM

Members more

  Béatrice Brousse Myriam Cayre Karine Magalon
Pascale Durbec
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Pascale Durbec

Researcher

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Oceane Mercier

MSc student

Béatrice Brousse
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Béatrice Brousse

PhD student

Myriam Cayre
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Myriam Cayre

Researcher

Myriam Cayre, CNRS research director, is particularly invested in the characterization of mouse models of multiple sclerosis used in the team (model of focal demyelination of the corpus callosum in the lysolecithin model of intoxication and cuprizone model of experimental autoimmune encephalomyelitis). The effort is focused on identifying the cellular and molecular processes controlling the mobilization of endogenous progenitor cells in the repair process.

Karine Magalon
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Karine Magalon

Technical staff

Karine Magalon, Research Engineer, joined the team in 2005.She provides expertise is in Biochemistry, Cell Biology and Cell Imaging. She develops models for the team of organotypic and primary cultures. She is particularly involved in the characterization of factors that promote oligodendrocyte maturation and myelination.

Alumni

  • Magali Macchi
  • Fabienne Alfonsi
  • Mircea Bancila
  • Cristina Cantarella
  • Sandrine Courtes
  • Florence Jaouen
  • Xavier Morin
  • Gilberte Monti
  • Francoise Padilla
  • Elise Peyre
  • Julien Vernerey
  • Isabelle Virard

Overview

logo equipe Durbec
Model organism
Biological process studied
  • Stem cells and adult brain repair
Technical approaches
  • Small animal surgery
  • Models of demyelination
  • Confocal and electron microscopy, videomicroscopy
  • Functional Genomic Analysis
  • Primary culture and organotypic culture
  • Behavioral tests
Medical applications
  • Multiple sclerosis and brain plasticity