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Modulation of oligodendrocyte precursor cells differentiation fate during CNS remyelination

Objective

The aim of this project is to identify the microenviromental factors and their downstream cellular effectors determining the fate of adult CNS precursor cells which could be modulated in order to control remyelination process. Remyelination is the best example of regenerative processes in adult CNS, in which new myelin sheaths are restored to axons that have been demyelinated as a result of oligodendrocyte death. However, the efficiency of remyelination decreases with age and in multiple sclerosis, a disease that can afflict a patient for several decades, there is a progressive decline in remyelination. The consequence of remyelination failure is progressive loss of the chronically demyelinated axons. Therefore, there is an urgent need to understand the cellular and molecular mechanisms involved in remyelination. New oligodendrocytes are derived from proliferating oligodendrocyte precursor cells (OPCs). However, we have demonstrated, in the lineage fate mapping study, that this name does not fully reflect their differentiation potential; under appropriate conditions they can also give rise to astrocytes and Schwann cells. We demonstrated that Schwann cells, derived form OPCs, occupied almost exclusively the tissue around blood vessels in astrocyte-deficient areas. Therefore the hypothesis postulating the occurrence of specific niches creating microenvironment that regulate or determine the alternative fate of precursor cells during remyelination arises. Our vascular-niche hypothesis, which will be investigated, predicts a causative role of BMP pathway in prompting OPCs to differentiation into Schwann cells or in blocking them in the proliferation phase.

Field of science

  • /medical and health sciences/basic medicine/neurology/multiple sclerosis
  • /natural sciences/biological sciences/neurobiology

Call for proposal

FP7-PEOPLE-2009-RG
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Funding Scheme

MC-ERG - European Re-integration Grants (ERG)

Coordinator

INSTYTUT BIOLOGII DOSWIADCZALNEJ IM. M. NENCKIEGO POLSKIEJ AKADEMII NAUK
Address
Ul. Ludwika Pasteura 3
02 093 Warszawa
Poland
Activity type
Research Organisations
EU contribution
€ 45 000
Administrative Contact
Marta Rucinska (Mrs.)