Abstract
Schwann cells are an important cell source for regenerative therapy for neural disorders. We investigated the role of the transcription factor sex determining region Y (SRY)-box 10 (SOX10) in the proliferation and myelination of Schwann cells. SOX10 is predominantly expressed in rat sciatic nerve-derived Schwann cells and is induced shortly after birth. Among transcription factors known to be important for the differentiation of Schwann cells, SOX10 potently transactivates the S100B promoter. In cultures of Schwann cells, overexpressing SOX10 dramatically induces S100B expression, while knocking down SOX10 with shRNA suppresses S100B expression. Here, we identify three core response elements of SOX10 in the S100B promoter and intron 1 with a putative SOX motif. Knockdown of either SOX10 or S100B enhances the proliferation of Schwann cells. In addition, using dissociated cultures of dorsal root ganglia, we demonstrate that suppressing S100B with shRNA impairs myelination of Schwann cells. These results suggest that the SOX10-S100B signaling axis critically regulates Schwann cell proliferation and myelination, and therefore is a putative therapeutic target for neuronal disorders.
Highlights
Schwann cells have recently attracted great attention as a cell source for regenerative therapy for various kinds of neuronal disorders
The expression of S100B gradually increases during Schwann cell differentiation [15, 16], and we previously reported that S100B expression is induced by SOX9 in chondrocytes [17]
When we suppressed SOX10 expression with a specific shRNA, the expression of S100B and Mpz was significantly suppressed (Fig. 3). These results suggest that SOX10 regulates S100B expression in Schwann cells
Summary
Schwann cells have recently attracted great attention as a cell source for regenerative therapy for various kinds of neuronal disorders. The developmental expression pattern of Schwann cell differentiation markers such as S100, nerve growth factor receptor (NGFR, known as p75NTR), myelin associated glycoprotein (MAG), and myelin protein zero (MPZ, known as P0), as well as transcription factors such as SOX10, paired box 3 (PAX3), POU class 3 homeobox 1 (POU3F, known as Oct6), and early growth response 2 (EGR2, known as KROX20) have been extensively studied [2, 3]. SOX family transcription factors are known to be involved in determining cell fate. SOX9 and SOX10 are involved in neural crest cell (NCC) migration and subsequently determining cell fate between neurons and Schwann cells [4,5,6]. The exact role of SOX10 in Schwann cell development still remains elusive, SOX10 is expressed from the early NCC stage through all stages of Schwann cell development and into adulthood [7]
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