TY  - JOUR
A1  - Weider, Matthias
A1  - Wegener, Amélie
A1  - Schmitt, Christian
A1  - Küspert, Melanie
A1  - Hillgärtner, Simone
A1  - Bösl, Michael R.
A1  - Hermans-Borgmeyer, Irm
A1  - Nait-Oumesmar, Brahim
A1  - Wegner, Michael
T1  - Elevated in vivo levels of a single transcription factor directly convert satellite glia into oligodendrocyte-like cells
JF  - PLoS Genetics
N2  - Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction. Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis, and their replenishment by reprogramming or cell conversion strategies is an important research aim. Using a transgenic approach we increased levels of the transcription factor Sox10 throughout the mouse embryo and thereby prompted Fabp7-positive glial cells in dorsal root ganglia of the peripheral nervous system to convert into cells with oligodendrocyte characteristics including myelin gene expression. These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage. Instead, Sox10 directly induced key elements of the regulatory network of differentiating oligodendrocytes, including Olig2, Olig1, Nkx2.2 and Myrf. An upstream enhancer mediated the direct induction of the Olig2 gene. Unlike Sox10, Olig2 was not capable of generating oligodendrocyte-like cells in dorsal root ganglia. Our findings provide proof-of-concept that Sox10 can convert conducive cells into oligodendrocyte-like cells in vivo and delineates options for future therapeutic strategies.
KW  - peripheral nervous system
KW  - Hirschsprung disease
KW  - spinal-cord
KW  - boundary cap
KW  - differentiation
KW  - stem cells
KW  - factor Sox10
KW  - mouse model
KW  - expression
KW  - Olig2
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144123
VL  - 11
IS  - 2
ER  - 
TY  - JOUR
A1  - Leopold, Stephanie A.
A1  - Zeilbeck, Ludwig F.
A1  - Weber, Gregor
A1  - Seitz, Roswitha
A1  - Bösl, Michael R.
A1  - Jägle, Herbert
A1  - Fuchshofer, Rudolf
A1  - Tamm, Ernst R.
A1  - Ohlmann, Andreas
T1  - Norrin protects optic nerve axons from degeneration in a mouse model of glaucoma
JF  - Scientific Reports
N2  - Norrin is a secreted signaling molecule activating the Wnt/β-catenin pathway. Since Norrin protects retinal neurons from experimental acute injury, we were interested to learn if Norrin attenuates chronic damage of retinal ganglion cells (RGC) and their axons in a mouse model of glaucoma. Transgenic mice overexpressing Norrin in the retina (Pax6-Norrin) were generated and crossed with DBA/2J mice with hereditary glaucoma and optic nerve axonal degeneration. One-year old DBA/2J/Pax6-Norrin animals had significantly more surviving optic nerve axons than their DBA/2J littermates. The protective effect correlated with an increase in insulin-like growth factor (IGF)-1 mRNA and an enhanced Akt phosphorylation in DBA/2J/Pax6-Norrin mice. Both mouse strains developed an increase in intraocular pressure during the second half of the first year and marked degenerative changes in chamber angle, ciliary body and iris structure. The degenerations were slightly attenuated in the chamber angle of DBA/2J/Pax6-Norrin mice, which showed a β-catenin increase in the trabecular meshwork. We conclude that high levels of Norrin and the subsequent constitutive activation of Wnt/β-catenin signaling in RGC protect from glaucomatous axonal damage via IGF-1 causing increased activity of PI3K-Akt signaling. Our results identify components of a protective signaling network preventing degeneration of optic nerve axons in glaucoma.
KW  - glaucoma
KW  - neurotrophic factors
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173494
VL  - 7
ER  -