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The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes.

Hornig J, Fröb F, Vogl MR, Hermans-Borgmeyer I, Tamm ER, Wegner M - PLoS Genet. (2013)

Bottom Line: Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes.This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination.Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.

ABSTRACT
Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.

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Consequences of CNS-specific Sox10 deletion on the expression of marker proteins of differentiating OL.(A–X) Immunohistochemistry was performed on transverse spinal cord sections from the forelimb region of wildtype (wt) (A–C,G–I,M–O,S–U) or Sox10ΔCNS (ko) (D–F,J–L,P–R,V–X) mice at P3 (A,D,G,J,M,P,S,V), P7 (B,E,H,K,N,Q,T,W) and P14 (C,F,I,L,O,R,U,X) using antibodies directed against Myrf (A–F), CC1 (G–L), CNPase (M–R), and Nkx2.2 (S–X). Ventral horn region is shown. Scale bar, 75 µm. (Y,Z) From these stainings, the total number of Myrf-positive (Y) and Nkx2.2-positive cells in the white matter (Z) was quantified in wildtype (black bars) and Sox10ΔCNS (white bars) mice. At least 9 separate sections from the forelimb region of 3 independent specimens were counted for each age and genotype. Data are presented as mean ± SEM for biological replicates. Differences to the wildtype were statistically significant for oligodendroglial cell numbers between wildtype and mutant from P3 onwards as determined by the Student's t test (*, P≤0.05; ***, P≤0.001).
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pgen-1003907-g003: Consequences of CNS-specific Sox10 deletion on the expression of marker proteins of differentiating OL.(A–X) Immunohistochemistry was performed on transverse spinal cord sections from the forelimb region of wildtype (wt) (A–C,G–I,M–O,S–U) or Sox10ΔCNS (ko) (D–F,J–L,P–R,V–X) mice at P3 (A,D,G,J,M,P,S,V), P7 (B,E,H,K,N,Q,T,W) and P14 (C,F,I,L,O,R,U,X) using antibodies directed against Myrf (A–F), CC1 (G–L), CNPase (M–R), and Nkx2.2 (S–X). Ventral horn region is shown. Scale bar, 75 µm. (Y,Z) From these stainings, the total number of Myrf-positive (Y) and Nkx2.2-positive cells in the white matter (Z) was quantified in wildtype (black bars) and Sox10ΔCNS (white bars) mice. At least 9 separate sections from the forelimb region of 3 independent specimens were counted for each age and genotype. Data are presented as mean ± SEM for biological replicates. Differences to the wildtype were statistically significant for oligodendroglial cell numbers between wildtype and mutant from P3 onwards as determined by the Student's t test (*, P≤0.05; ***, P≤0.001).

Mentions: The reduction in Myrf expression was not only observed on transcript but also on protein level (compare Figure 3A–C to Figure 3D–F, and for quantitation Figure 3Y), and resembled the markedly reduced expression of the early oligodendroglial differentiation marker CC1 (Figure 3G–L). Expression of 2′,3′-cyclic nucleotide 3′ phosphodiesterase (CNPase) was drastically reduced as well (Figure 3M–R). Two markers of the promyelinating stage, in contrast, exhibited only mild (Nkx2.2) or no (Gpr17) alterations in Sox10ΔCNS mice (Figure 3S-X-,Z and Figure S3A).


The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes.

Hornig J, Fröb F, Vogl MR, Hermans-Borgmeyer I, Tamm ER, Wegner M - PLoS Genet. (2013)

Consequences of CNS-specific Sox10 deletion on the expression of marker proteins of differentiating OL.(A–X) Immunohistochemistry was performed on transverse spinal cord sections from the forelimb region of wildtype (wt) (A–C,G–I,M–O,S–U) or Sox10ΔCNS (ko) (D–F,J–L,P–R,V–X) mice at P3 (A,D,G,J,M,P,S,V), P7 (B,E,H,K,N,Q,T,W) and P14 (C,F,I,L,O,R,U,X) using antibodies directed against Myrf (A–F), CC1 (G–L), CNPase (M–R), and Nkx2.2 (S–X). Ventral horn region is shown. Scale bar, 75 µm. (Y,Z) From these stainings, the total number of Myrf-positive (Y) and Nkx2.2-positive cells in the white matter (Z) was quantified in wildtype (black bars) and Sox10ΔCNS (white bars) mice. At least 9 separate sections from the forelimb region of 3 independent specimens were counted for each age and genotype. Data are presented as mean ± SEM for biological replicates. Differences to the wildtype were statistically significant for oligodendroglial cell numbers between wildtype and mutant from P3 onwards as determined by the Student's t test (*, P≤0.05; ***, P≤0.001).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3814293&req=5

pgen-1003907-g003: Consequences of CNS-specific Sox10 deletion on the expression of marker proteins of differentiating OL.(A–X) Immunohistochemistry was performed on transverse spinal cord sections from the forelimb region of wildtype (wt) (A–C,G–I,M–O,S–U) or Sox10ΔCNS (ko) (D–F,J–L,P–R,V–X) mice at P3 (A,D,G,J,M,P,S,V), P7 (B,E,H,K,N,Q,T,W) and P14 (C,F,I,L,O,R,U,X) using antibodies directed against Myrf (A–F), CC1 (G–L), CNPase (M–R), and Nkx2.2 (S–X). Ventral horn region is shown. Scale bar, 75 µm. (Y,Z) From these stainings, the total number of Myrf-positive (Y) and Nkx2.2-positive cells in the white matter (Z) was quantified in wildtype (black bars) and Sox10ΔCNS (white bars) mice. At least 9 separate sections from the forelimb region of 3 independent specimens were counted for each age and genotype. Data are presented as mean ± SEM for biological replicates. Differences to the wildtype were statistically significant for oligodendroglial cell numbers between wildtype and mutant from P3 onwards as determined by the Student's t test (*, P≤0.05; ***, P≤0.001).
Mentions: The reduction in Myrf expression was not only observed on transcript but also on protein level (compare Figure 3A–C to Figure 3D–F, and for quantitation Figure 3Y), and resembled the markedly reduced expression of the early oligodendroglial differentiation marker CC1 (Figure 3G–L). Expression of 2′,3′-cyclic nucleotide 3′ phosphodiesterase (CNPase) was drastically reduced as well (Figure 3M–R). Two markers of the promyelinating stage, in contrast, exhibited only mild (Nkx2.2) or no (Gpr17) alterations in Sox10ΔCNS mice (Figure 3S-X-,Z and Figure S3A).

Bottom Line: Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes.This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination.Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.

ABSTRACT
Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.

Show MeSH
Related in: MedlinePlus