Limits...
Olig2 regulates Sox10 expression in oligodendrocyte precursors through an evolutionary conserved distal enhancer.

Küspert M, Hammer A, Bösl MR, Wegner M - Nucleic Acids Res. (2010)

Bottom Line: We found that U2 was active in oligodendrocyte precursors, but not in mature oligodendrocytes.U2 activity also did not mediate the initial Sox10 induction after specification arguing that Sox10 expression during oligodendroglial development depends on the activity of multiple regulatory regions.Considering the selective expression of Nkx6.2 at the time of specification and in differentiated oligodendrocytes, Nkx6.2 may be involved in limiting U2 activity to the precursor stage during oligodendrocyte development.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.

ABSTRACT
The HMG-domain transcription factor Sox10 is expressed throughout oligodendrocyte development and is an important component of the transcriptional regulatory network in these myelin-forming CNS glia. Of the known Sox10 regulatory regions, only the evolutionary conserved U2 enhancer in the distal 5'-flank of the Sox10 gene exhibits oligodendroglial activity. We found that U2 was active in oligodendrocyte precursors, but not in mature oligodendrocytes. U2 activity also did not mediate the initial Sox10 induction after specification arguing that Sox10 expression during oligodendroglial development depends on the activity of multiple regulatory regions. The oligodendroglial bHLH transcription factor Olig2, but not the closely related Olig1 efficiently activated the U2 enhancer. Olig2 bound U2 directly at several sites including a highly conserved one in the U2 core. Inactivation of this site abolished the oligodendroglial activity of U2 in vivo. In contrast to Olig2, the homeodomain transcription factor Nkx6.2 repressed U2 activity. Repression may involve recruitment of Nkx6.2 to U2 and inactivation of Olig2 and other activators by protein-protein interactions. Considering the selective expression of Nkx6.2 at the time of specification and in differentiated oligodendrocytes, Nkx6.2 may be involved in limiting U2 activity to the precursor stage during oligodendrocyte development.

Show MeSH

Related in: MedlinePlus

The U2-lacZ transgene is expressed in embryonic and early post-natal spinal cord. LacZ expression was detected colorimetrically using X-gal substrate on transverse sections from the forelimb level of Sox10lacZ/+ (A, C, E, G and I) and age-matched U2-lacZ (B, D, F, H and J) mice at 12.5 dpc (A and B), 14.5 dpc (C and D), 16.5 dpc (E and F), P1 (G and H) and P14 (I and J). The pMN domain as the main origin for spinal cord OLPs is highlighted in A and C by an arrow. Arrowheads in G and H point to the marginal zone. No lacZ staining was detected in wild-type littermates under identical conditions. Size bars correspond to 200 µm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3045606&req=5

Figure 1: The U2-lacZ transgene is expressed in embryonic and early post-natal spinal cord. LacZ expression was detected colorimetrically using X-gal substrate on transverse sections from the forelimb level of Sox10lacZ/+ (A, C, E, G and I) and age-matched U2-lacZ (B, D, F, H and J) mice at 12.5 dpc (A and B), 14.5 dpc (C and D), 16.5 dpc (E and F), P1 (G and H) and P14 (I and J). The pMN domain as the main origin for spinal cord OLPs is highlighted in A and C by an arrow. Arrowheads in G and H point to the marginal zone. No lacZ staining was detected in wild-type littermates under identical conditions. Size bars correspond to 200 µm.

Mentions: We, therefore, compared the U2-lacZ expression pattern in the spinal cord at various days of embryonic and post-natal development with lacZ expression from the Sox10lacZ allele that faithfully mimicks Sox10 expression (13). Whereas OLPs were already visible at 12.5 dpc by X-gal staining near the pMN domain in spinal cords of Sox10+/lacZ embryos (Figure 1A, arrow), age-matched spinal cords of U2-lacZ transgenic embryos exhibited no X-gal staining within the spinal cord (Figure 1B). In contrast, X-gal staining was comparable in both genotypes outside the spinal cord in dorsal root ganglia and along peripheral nerves (Figure 1A and B). At 12.75 dpc X-gal staining started to become detectable in U2-lacZ transgenic embryos but only in Sox10-positive cells that had migrated some distance from the ventricular zone (Figure 2A and A′). At 14.5 dpc, a high number of lacZ-positive cells was detectable in U2-lacZ and Sox10+/lacZ embryos (Figure 1C and D). In both genotypes, OLPs were stained throughout the spinal cord parenchyma. In Sox10+/lacZ embryos, the origin of OLPs was still marked by a particular high density of X-gal stained cells near the pMN domain (Figure 1C, arrow). This staining was again missing in the U2-lacZ embryos (Figure 1D). Compared to lacZ expression in Sox10+/lacZ embryos, the U2-lacZ transgene is thus turned on in the oligodendrocyte lineage with delay.Figure 1.


Olig2 regulates Sox10 expression in oligodendrocyte precursors through an evolutionary conserved distal enhancer.

Küspert M, Hammer A, Bösl MR, Wegner M - Nucleic Acids Res. (2010)

The U2-lacZ transgene is expressed in embryonic and early post-natal spinal cord. LacZ expression was detected colorimetrically using X-gal substrate on transverse sections from the forelimb level of Sox10lacZ/+ (A, C, E, G and I) and age-matched U2-lacZ (B, D, F, H and J) mice at 12.5 dpc (A and B), 14.5 dpc (C and D), 16.5 dpc (E and F), P1 (G and H) and P14 (I and J). The pMN domain as the main origin for spinal cord OLPs is highlighted in A and C by an arrow. Arrowheads in G and H point to the marginal zone. No lacZ staining was detected in wild-type littermates under identical conditions. Size bars correspond to 200 µm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045606&req=5

Figure 1: The U2-lacZ transgene is expressed in embryonic and early post-natal spinal cord. LacZ expression was detected colorimetrically using X-gal substrate on transverse sections from the forelimb level of Sox10lacZ/+ (A, C, E, G and I) and age-matched U2-lacZ (B, D, F, H and J) mice at 12.5 dpc (A and B), 14.5 dpc (C and D), 16.5 dpc (E and F), P1 (G and H) and P14 (I and J). The pMN domain as the main origin for spinal cord OLPs is highlighted in A and C by an arrow. Arrowheads in G and H point to the marginal zone. No lacZ staining was detected in wild-type littermates under identical conditions. Size bars correspond to 200 µm.
Mentions: We, therefore, compared the U2-lacZ expression pattern in the spinal cord at various days of embryonic and post-natal development with lacZ expression from the Sox10lacZ allele that faithfully mimicks Sox10 expression (13). Whereas OLPs were already visible at 12.5 dpc by X-gal staining near the pMN domain in spinal cords of Sox10+/lacZ embryos (Figure 1A, arrow), age-matched spinal cords of U2-lacZ transgenic embryos exhibited no X-gal staining within the spinal cord (Figure 1B). In contrast, X-gal staining was comparable in both genotypes outside the spinal cord in dorsal root ganglia and along peripheral nerves (Figure 1A and B). At 12.75 dpc X-gal staining started to become detectable in U2-lacZ transgenic embryos but only in Sox10-positive cells that had migrated some distance from the ventricular zone (Figure 2A and A′). At 14.5 dpc, a high number of lacZ-positive cells was detectable in U2-lacZ and Sox10+/lacZ embryos (Figure 1C and D). In both genotypes, OLPs were stained throughout the spinal cord parenchyma. In Sox10+/lacZ embryos, the origin of OLPs was still marked by a particular high density of X-gal stained cells near the pMN domain (Figure 1C, arrow). This staining was again missing in the U2-lacZ embryos (Figure 1D). Compared to lacZ expression in Sox10+/lacZ embryos, the U2-lacZ transgene is thus turned on in the oligodendrocyte lineage with delay.Figure 1.

Bottom Line: We found that U2 was active in oligodendrocyte precursors, but not in mature oligodendrocytes.U2 activity also did not mediate the initial Sox10 induction after specification arguing that Sox10 expression during oligodendroglial development depends on the activity of multiple regulatory regions.Considering the selective expression of Nkx6.2 at the time of specification and in differentiated oligodendrocytes, Nkx6.2 may be involved in limiting U2 activity to the precursor stage during oligodendrocyte development.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.

ABSTRACT
The HMG-domain transcription factor Sox10 is expressed throughout oligodendrocyte development and is an important component of the transcriptional regulatory network in these myelin-forming CNS glia. Of the known Sox10 regulatory regions, only the evolutionary conserved U2 enhancer in the distal 5'-flank of the Sox10 gene exhibits oligodendroglial activity. We found that U2 was active in oligodendrocyte precursors, but not in mature oligodendrocytes. U2 activity also did not mediate the initial Sox10 induction after specification arguing that Sox10 expression during oligodendroglial development depends on the activity of multiple regulatory regions. The oligodendroglial bHLH transcription factor Olig2, but not the closely related Olig1 efficiently activated the U2 enhancer. Olig2 bound U2 directly at several sites including a highly conserved one in the U2 core. Inactivation of this site abolished the oligodendroglial activity of U2 in vivo. In contrast to Olig2, the homeodomain transcription factor Nkx6.2 repressed U2 activity. Repression may involve recruitment of Nkx6.2 to U2 and inactivation of Olig2 and other activators by protein-protein interactions. Considering the selective expression of Nkx6.2 at the time of specification and in differentiated oligodendrocytes, Nkx6.2 may be involved in limiting U2 activity to the precursor stage during oligodendrocyte development.

Show MeSH
Related in: MedlinePlus