Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10

Abstract

Sox10 is a high-mobility-group transcriptional regulator in early neural crest. Without Sox10, no glia develop throughout the peripheral nervous system. Here we show that Sox10 is restricted in the central nervous system to myelin-forming oligodendroglia. In Sox10-deficient mice progenitors develop, but terminal differentiation is disrupted. No myelin was generated upon transplantation of Sox10-deficient neural stem cells into wild-type hosts showing the permanent, cell-autonomous nature of the defect. Sox10 directly regulates myelin gene expression in oligodendrocytes, but does not control erbB3 expression as in peripheral glia. Sox10 thus functions in peripheral and central glia at different stages and through different mechanisms.

BMP signaling mutant mice exhibit glial cell maturation defects

“…If the oligodendrocyte precursors were unable to mature or were delayed in maturation, the O4 number would stay the same. Finally, these data mirror those found in mice with genetically eliminated expression of Olig1, Nkx2.2, Sox 10, transcription factors required for oligodendrocyte development (Lu et al, 2002;Qi et al, 2001;Stolt et al, 2002). These knockout models showed normal numbers of OPCs and delayed or decreased oligodendrocyte differentiation without adoption of another cell fate.…”

Differential and cooperative actions of Olig1 and Olig2 transcription factors on immature proliferating cells after contusive spinal cord injury

“…Sox9 and Sox10 are two highly related group E Sox proteins, and both are implicated in OL development, but at different stages. Sox9 is known to exert a strong influence on the initial specification of OLs (Stolt et al, 2003), whereas Sox10 plays a key role in promoting terminal OL differentiation (Li et al, 2007a;Stolt et al, 2002). We found that overexpression of Olig1 and Olig2 resulted in a significant increase in Sox9 expression (P < 0.05 vs. GFP group and P < 0.01 vs. Olig1 group) (Fig.…”

“…6C). It has been reported that Sox10 plays a key role in promoting terminal OL differentiation and it also regulates MBP gene expression directly or in combination with Olig1 (Li et al, 2007a;Stolt et al, 2002). The proportion of Sox10 positive cells was also markedly increased by Olig1 and Olig2 overexpression in the injured spinal cord, suggesting that the robust effects of Olig1 and Olig2 on OL maturation may be mediated by Sox10.…”

Expression of Sox transcription factors in the developing mouse pancreas

“…Recently, several Sox genes have been recognized as key players in the regulation of embryonic development and cell fate determination. The analysis of Sox gene mutations in humans, mice, and zebrafish have demonstrated a role for Sox genes in endoderm specification, as well as the development of gonads, lens, heart, lymphocytes, bone, and glial cells (Kent et al, 1996;Schilham et al, 1996;Britsch et al, 2001;Dickmeis et al, 2001;Kamachi et al, 2001;Lefebvre et al, 2001;Stolt et al, 2002). Despite their broad function in embryonic development, the expression and function of Sox genes during development of the pancreas remain to be explored.…”