Brain Research Institute
Central nervous system (CNS) injuries are particularly traumatic owing to the limited capabilities of the CNS for repair. Recent evidence however suggests that an intrinsic capability of the CNS for repair exist, but that it is repressed in most regions.
Self-repair of the lesioned CNS may be achieved by two processes:
(i) generation of new cells (neurons and/or oligodendrocytes) for replacement of the lost ones;
(ii) anatomical reorganization of the neurons that has been left intact by the lesion.
Our research aims at approaching these questions in parallel in order to develop new approaches to promote functional repair of the adult CNS in injuries or in pathologies.
Keywords: neurogenesis, oligodendrogenesis, proneural bHLH transcription factors, adult neurogenic regions, spinal cord and cortical injuries, neural stem/progenitor cells response to injuries, anatomical plasticity
3 postdoctoral fellows, 2 PhD students
We have shown that the rodent motor system is capable of significant reorganization after injury. More recently we have been interested in understanding the transcriptional codes acting in the adult neurogenic regions where neurons are continuously produced during the entire life of the animal, mature and functionally integrate in pre-existing neuronal network. We have shown that proneural bHLH transcription factors are expressed in defined progenitor populations in adult neurogenic regions. We have taken advantage of the specific expression of these factors to conditionally and specifically label newborn neurons. Furthermore, we have shown that proneural bHLH transcription factor over-expression in progenitor cells is necessary but not sufficient to promote the neuronal differentiation of these cells outside of adult neurogenic regions. We have identified a central mechanism mediating the inhibition of proneural protein activity in these regions, and developed strategies to overcome it.
We will continue our efforts to 1) understand the pattern of expression, function and regulation of bHLH proteins in adult neurogenic regions, 2) produce “dominant active forms of bHLH transcription factors (proneural and pro-oligodendroglial) to favor cellular replacement after CNS injuries, 3) investigate the capacities and limitation of the CNS to functionally reorganize after trauma.
Various culture techniques: neural stem cell cultures (neurospheres and adherent cultures), Organotypic slices cultures, overlay assay
Electroporation in vitro and in vivo
Various techniques of microsurgery, tract tracing, behavioral testing
Various techniques of transgenesis: viral transduction, Cre-lox, conditional Cre mice
Electrophysiological recordings (patch clamping) in collaboration with Prof Urs Gerber
NCCR Neural stem Cells, Hartmann Muller foundation, Dr Scholl Foundation, IFRP-Zurich, Newton Trust, MRC-UK, ZNZ.
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