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XI European Meeting on Glial Cell Function in Health and Disease

Overview Session Overview Sessionprint print  
 

July 3, 2013 - Room 1 9:00am - 10:55am
Workshop II: In Vivo Analysis of Glial Cells: Promises and Pitfalls of Genetic Manipulation

Organized by
Dwight E. Bergles (Johns Hopkins University, Baltimore, USA)

9:00am

Introduction

*Dwight Bergles 1
1 Johns Hopkins University, , Baltimore, United States
Abstract text :

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9:10am
W02-01

Mouse models to study adult oligodendrocyte progenitor cells: Their limitations and benefits

*Leda Dimou 1,2
1 Ludwig-Maximilians University, Institute of Physiology, Munich, Germany
2 Helmholtz Zentrum Munich, Institute for Stem Cell Research, Neuherberg, Germany
Abstract text :

Oligodendrocyte progenitor cells (OPCs), also known as NG2 -cells, are an abundant cell population of the adult brain and the only proliferating cells outside the neurogenic niches. However, their functions in the adult CNS and the mechanisms regulating their behavior under both physiological and pathological conditions are still not resolved. We characterized their proliferative properties, such as cell cycle length, proliferative fraction, self-renewal and progeny in the healthy brain. Our data show that adult OPCs have a long cell cycle and that many of them can self-renew. Analysis of the progeny of these cells by genetic fate mapping analysis with the help of tamoxifen inducible Cre-recombination in the Olig2-locus revealed regional differences in their differentiation properties, with OPCs in the WM to preferentially differentiate into mature, myelinating oligodendrocytes. When we compared these data with BrdU labeling retaining experiments, we could show that GM OPCs with high levels of Olig2 are more prone to remain progenitors.


To overcome the low recombination efficiency in the Olig2CreERTm mice, labeling mainly OPCs with high Olig2-levels, we generated a new BAC transgenic mouse expressing the inducible form of iCre-recombinase (iCreERT2) in the locus of the transcription factor Sox10, allowing a precisely timed recombination in NG2 -cells as well as oligodendrocytes with a very high efficiency.


To further understand the roles of OPCs, we analyzed their properties also after two distinct stimuli, acute invasive brain injury and increased physiological activity by voluntary physical exercise. We could show that after cortical stab wound injury many of the OPCs re-entered the cell cycle very fast, consistent with their reactive capacity. In striking contrast, voluntary physical exercise showed the opposite effect with increased exit of the cell cycle followed by an enhanced and fast differentiation into mature oligodendrocytes. Notably, after these stimuli, the progeny of NG2 -cells always remained within the oligodendrocyte lineage. Taken together, our data demonstrate that the endogenous population of adult brain parenchymal OPCs is subject to profound modulation by environmental stimuli in both directions, either faster proliferation or faster differentiation.



9:45am
W02-02

Of mice and man: Prospects and limitations of glial disease models

*Sandra Goebbels 1 , Klaus-Armin Nave 1
1 Max Planck Institute of Experimental Medicine, Department of Neurogenetics, Goettingen, Germany
Abstract text :

The systematic generation of transgenic, conventional and conditional mouse models for human neurodegenerative diseases and psychiatric syndromes has provided surprising results as to what extent disease subphenotypes resemble the human clinical picture. We will discuss different mouse mutants affecting glia cell function and discuss their applicability in modeling diseases as different as X-linked Adrenoleukodystrophy and Schizophrenia.



10:20am
W02-03

Inducible Cre mice for manipulating oligodendrocytes: promises and problems.

*Brian Popko 1
1 The University of Chicago, , Chicago, United States
Abstract text :

The manipulation of gene expression using Cre-lox technology is a powerful approach for the study of gene function in a cell-specific manner.  Moreover, the use of an inducible form of the Cre recombinase allows for the temporal control of gene activity, such that gene function can be assessed at predetermined time points during development and in adults.  These approaches have proven particularly useful in the analysis of the myelination and remyelination processes.  Nevertheless, these systems are complex and require careful consideration of controls.  We have used an inducible Cre approach to generate a mouse model of adult-onset oligodendrocyte loss and demyelination that demonstrates robust remyelination.  I will discus this model in the context of the Cre-lox technology.