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The transcription factor Sox5 modulates Sox10 function during melanocyte development.

Stolt CC, Lommes P, Hillgärtner S, Wegner M - Nucleic Acids Res. (2008)

Bottom Line: The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia.This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation.Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Fahrstrasse 17, D-91054 Erlangen, Germany.

ABSTRACT
The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia. Here, we show in mouse that Sox5 expression also continues after neural crest specification in the melanocyte lineage. Despite its continued expression, Sox5 has little impact on melanocyte development on its own as generation of melanoblasts and melanocytes is unaltered in Sox5-deficient mice. Loss of Sox5, however, partially rescued the strongly reduced melanoblast generation and marker gene expression in Sox10 heterozygous mice arguing that Sox5 functions in the melanocyte lineage by modulating Sox10 activity. This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation. Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

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Sox gene expression in melanoblasts. Expression of Sox5 (A, C, I and K), its long isoforms (E and G), Sox6 (M and O), Sox13 (Q and S) and Sox9 (U and W) (all shown in red) was compared to occurrence of Sox10 (B, C, F and G) and Mitf (J, K, N, O, R, S, V and W) (both shown in green) by co-immunohistochemistry on transverse sections from the forelimb region of wild-type embryos at 11.5 dpc. To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L, P, T and X).
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Figure 1: Sox gene expression in melanoblasts. Expression of Sox5 (A, C, I and K), its long isoforms (E and G), Sox6 (M and O), Sox13 (Q and S) and Sox9 (U and W) (all shown in red) was compared to occurrence of Sox10 (B, C, F and G) and Mitf (J, K, N, O, R, S, V and W) (both shown in green) by co-immunohistochemistry on transverse sections from the forelimb region of wild-type embryos at 11.5 dpc. To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L, P, T and X).

Mentions: Sox5 had previously been detected in the early migrating neural crest of chicken (15) and is similarly expressed in the mouse neural crest (C.S. and M.W., unpublished data). To study whether Sox5 expression continues in those migrating neural crest cells that become specified to melanoblasts, we performed colabeling studies on mouse embryos at 11.5 dpc (Figure 1). Using antibodies directed against Sox10, migrating neural crest-derived cells were identified in the trunk region immediately below the epidermis (Figure 1B, C, F and G). These cells were also labeled by Sox5-specific antibodies including those that recognized all Sox5 isoforms (Figure 1A and C) and those that specifically recognized the long Sox5 isoforms (Figure 1E and G). To confirm that these Sox5-positive neural crest-derived cells corresponded to melanoblasts, we performed additional colabeling with antibodies directed against Mitf (Figure 1J). Significant amounts of Sox5 were present in Mitf-positive cells (Figure 1I) indicating that Sox5 is indeed expressed in the melanocyte lineage (Figure 1K and L). The melanocyte lineage thus represents one of several cell types in which Sox5 and Sox10 are coexpressed (9,16).Figure 1


The transcription factor Sox5 modulates Sox10 function during melanocyte development.

Stolt CC, Lommes P, Hillgärtner S, Wegner M - Nucleic Acids Res. (2008)

Sox gene expression in melanoblasts. Expression of Sox5 (A, C, I and K), its long isoforms (E and G), Sox6 (M and O), Sox13 (Q and S) and Sox9 (U and W) (all shown in red) was compared to occurrence of Sox10 (B, C, F and G) and Mitf (J, K, N, O, R, S, V and W) (both shown in green) by co-immunohistochemistry on transverse sections from the forelimb region of wild-type embryos at 11.5 dpc. To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L, P, T and X).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553580&req=5

Figure 1: Sox gene expression in melanoblasts. Expression of Sox5 (A, C, I and K), its long isoforms (E and G), Sox6 (M and O), Sox13 (Q and S) and Sox9 (U and W) (all shown in red) was compared to occurrence of Sox10 (B, C, F and G) and Mitf (J, K, N, O, R, S, V and W) (both shown in green) by co-immunohistochemistry on transverse sections from the forelimb region of wild-type embryos at 11.5 dpc. To visualize the region in which double positive cells were found, nuclei were counterstained with DAPI (D, H, L, P, T and X).
Mentions: Sox5 had previously been detected in the early migrating neural crest of chicken (15) and is similarly expressed in the mouse neural crest (C.S. and M.W., unpublished data). To study whether Sox5 expression continues in those migrating neural crest cells that become specified to melanoblasts, we performed colabeling studies on mouse embryos at 11.5 dpc (Figure 1). Using antibodies directed against Sox10, migrating neural crest-derived cells were identified in the trunk region immediately below the epidermis (Figure 1B, C, F and G). These cells were also labeled by Sox5-specific antibodies including those that recognized all Sox5 isoforms (Figure 1A and C) and those that specifically recognized the long Sox5 isoforms (Figure 1E and G). To confirm that these Sox5-positive neural crest-derived cells corresponded to melanoblasts, we performed additional colabeling with antibodies directed against Mitf (Figure 1J). Significant amounts of Sox5 were present in Mitf-positive cells (Figure 1I) indicating that Sox5 is indeed expressed in the melanocyte lineage (Figure 1K and L). The melanocyte lineage thus represents one of several cell types in which Sox5 and Sox10 are coexpressed (9,16).Figure 1

Bottom Line: The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia.This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation.Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Fahrstrasse 17, D-91054 Erlangen, Germany.

ABSTRACT
The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia. Here, we show in mouse that Sox5 expression also continues after neural crest specification in the melanocyte lineage. Despite its continued expression, Sox5 has little impact on melanocyte development on its own as generation of melanoblasts and melanocytes is unaltered in Sox5-deficient mice. Loss of Sox5, however, partially rescued the strongly reduced melanoblast generation and marker gene expression in Sox10 heterozygous mice arguing that Sox5 functions in the melanocyte lineage by modulating Sox10 activity. This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation. Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.

Show MeSH
Related in: MedlinePlus