der Medizinischen Fakultät im Emil-Fischer-Centrum

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AG Stolt

Leitung: PD Dr. Claus Stolt

Role of SoxD transcription factors in nervous system development

My group is interested in the characterization of SoxD protein function during nervous system development. Members of group D (Sox5, Sox6, Sox13) of the Sox protein family are only distantly related to group E Sox proteins (Sox8, Sox9, Sox10). Nevertheless, members of both groups are expressed together in diverse cell types and tissues and are e.g. able to synergistically regulate target genes in chondrocytes.

Our work addresses the functional interaction between SoxD and SoxE proteins focusing on the developing embryonic spinal cord and forebrain. Using Sox5- and Sox6-deficient mice, we found that Sox5 and Sox6 can modulate the key functions of Sox9 or Sox10 during oligodendrocyte development. Sox5 and Sox6 counteract SoxE function in this cell population. They help to keep the oligodendrocyte precursors in an immature state and prevent their premature differentiation. A similar mode of action has also been determined for SoxD proteins in neural crest derivatives such as melanocytes. Here, SoxD proteins can compete with SoxE proteins for DNA binding as well as recruit transcriptional co-repressors to the regulatory regions of those genes that would otherwise be activated by SoxE proteins in a cell-specific manner.

For our analysis, transgenic, constitutive and conditional knockout mouse mutants are accessible. We are using methods of histology, molecular biology, and protein biochemistry as well as tissue culture methods or e.g. the in ovo electroporation. Our aim is to elucidate the developmental influence of Sox5, Sox6, and Sox13 on processes of neural differentiation, in particular the interplay with other transcription factors.

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