Sox10 and MRF: Interplay of two transcription factors as cornerstone of the regulatory network in myelinating oligodendrocytes
Third party funded individual grant
Start date :
01.01.2013
End date :
31.12.2016
Project details
Short description
Normal function of the vertebrate nervous
system requires rapid saltatory conduction along axons myelinated by
oligodendrocytes in the central and Schwann cells in the peripheral
nervous system. Sox10 is the only transcription factor identified so far
that is essential for myelination in both glial cell types. Whereas
Sox10 function during Schwann cell myelination has been characterized to
the molecular level, much less is known about its actions in
myelinating oligodendrocytes. Therefore this proposal aims to unravel
the molecular function of Sox10 within the regulatory network that
drives myelination in oligodendrocytes. Based on our preliminary
results, we will investigate the hypothesis that Sox10, possibly with
the help of supporting factors and the chromatin remodelling machinery,
induces expression of MRF as another transcription factor that once
induced, cooperates with its inducer Sox10 to activate myelin gene
expression and start the myelination program in oligodendrocytes. By
identifying target genes for Sox10, MRF and the combination of both on a
global scale, we will obtain unprecedented insights into the
myelination program and its underlying regulatory circuits. Our studies
will increase our knowledge about myelination and its regulation in
oligodendrocytes. They will help to better understand myelin disease
mechanisms and could be instrumental in developing strategies for
disease treatment.
Scientific Abstract
Normal function of the vertebrate nervous system requires rapid saltatory conduction along axons myelinated by oligodendrocytes in the central and Schwann cells in the peripheral nervous system. Sox10 is the only transcription factor identified so far that is essential for myelination in both glial cell types. Whereas Sox10 function during Schwann cell myelination has been characterized to the molecular level, much less is known about its actions in myelinating oligodendrocytes. Therefore this proposal aims to unravel the molecular function of Sox10 within the regulatory network that drives myelination in oligodendrocytes. Based on our preliminary results, we will investigate the hypothesis that Sox10, possibly with the help of supporting factors and the chromatin remodelling machinery, induces expression of MRF as another transcription factor that once induced, cooperates with its inducer Sox10 to activate myelin gene expression and start the myelination program in oligodendrocytes. By identifying target genes for Sox10, MRF and the combination of both on a global scale, we will obtain unprecedented insights into the myelination program and its underlying regulatory circuits. Our studies will increase our knowledge about myelination and its regulation in oligodendrocytes. They will help to better understand myelin disease mechanisms and could be instrumental in developing strategies for disease treatment.
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