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.
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.
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 (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.
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
May 8th, 2018
Promoting Myelin Repair through In Vivo Neuroblast Reprogramming
PUBLICATION
July 3rd, 2015
Region and dynamic specificities of adult neural stem cells and oligodendrocyte precursors in myelin regeneration in the mouse brain.
PUBLICATION
June 12th, 2014
Oligodendrogenesis in the normal and pathological central nervous system.
PUBLICATION
July 5th, 2013
Tubacin prevents neuronal migration defects and epileptic activity caused by rat Srpx2 silencing in utero.
PUBLICATION
July 3rd, 2013
Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination.
PUBLICATION
February 26th, 2013
Ciliary Neurotrophic Factor Controls Progenitor Migration during Remyelination in the Adult Rodent Brain.
PUBLICATION
January 30th, 2013
Sonic Hedgehog Signaling Is a Positive Oligodendrocyte Regulator during Demyelination.
PUBLICATION
February 1st, 2012
Olesoxime accelerates myelination and promotes repair in models of demyelination.
PUBLICATION
April 4th, 2011
A lateral belt of cortical LGN and NuMA guides mitotic spindle movements and planar division in neuroepithelial cells.
PUBLICATION
January 1st, 2011
RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres.
PUBLICATION
January 1st, 2011
Reelin controls progenitor cell migration in the healthy and pathological adult mouse brain.
PUBLICATION
May 3rd, 2009
Cell migration in the normal and pathological postnatal mammalian brain
PUBLICATION
February 1st, 2008
Intranasal HB-EGF administration favors adult SVZ cell mobilization to demyelinated lesions in mouse corpus callosum.
PUBLICATION
January 1st, 2008
LIFR beta plays a major role in neuronal identity determination and glial differentiation in the mouse facial nucleus.
PUBLICATION
January 1st, 2008
Characterization of heterogeneous glial cell populations involved in dehydration-induced proliferation in the adult rat neurohypophysis.
PUBLICATION
January 1st, 2008
In vitro migration assays of neural stem cells.
PUBLICATION
November 1st, 2007
Control of planar divisions by the G-protein regulator LGN maintains progenitors in the chick neuroepithelium.
PUBLICATION
August 1st, 2007
Relevance of combinatorial profiles of intermediate filaments and transcription factors for glioma histogenesis.
PUBLICATION
March 1st, 2007
PSA-NCAM in postnatally generated immature neurons of the olfactory bulb: a crucial role in regulating p75 expression and cell survival.
PUBLICATION
February 1st, 2007
Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models.
PUBLICATION
April 1st, 2006
Migrating and myelinating potential of subventricular zone neural progenitor cells in white matter tracts of the adult rodent brain.
PUBLICATION
April 1st, 2006
In vitro identification and functional characterization of glial precursor cells in human gliomas.
PUBLICATION
February 1st, 2006
Oligodendrocyte precursor cells generate pituicytes in vivo during neurohypophysis development.
PUBLICATION
October 1st, 2004
Migrating and myelinating potential of neural precursors engineered to overexpress PSA-NCAM.
PUBLICATION
July 1st, 2004
Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity.
PUBLICATION
January 1st, 2004
