Olig1 and Sox10 Interact Synergistically to DriveMyelin Basic ProteinTranscription in Oligodendrocytes

Abstract

The oligodendrocyte lineage genes (Olig1/2), encoding basic helix-loop-helix transcription factors, were first identified in screens for master regulators of oligodendrocyte development. OLIG1 is important for differentiation of oligodendrocyte precursors into myelinforming oligodendrocytes during development and is thought to play a crucial role in remyelination during multiple sclerosis. However, it is still unclear how OLIG1 interacts with its transcriptional cofactors and DNA targets. OLIG1 was reportedly restricted to mammals, but we demonstrate here that zebrafish and other teleosts also possess an OLIG1 homolog. In zebrafish, as in mammals, Olig1 is expressed in the oligodendrocyte lineage. Olig1 associates physically with another myelin-associated transcription factor, Sox10, and the Olig1/Sox10 complex activates mbp (myelin basic protein) transcription via conserved DNA sequence motifs in the mbp promoter region. In contrast, Olig2 does not bind to Sox10 in zebrafish, although both OLIG1 and OLIG2 bind SOX10 in mouse.

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.…”

“…Previous studies showed that a pair of related basic helix-loop-helix transcription factors, Olig1 and Olig2, is essential for generating OL lineage cells (Lu et al, 2000;Zhou and Anderson, 2002). Further studies have shown that both Olig1 and Olig2 in collaboration with other transcription factors are substantially involved during the later stages of OL differentiation and maturation (Fu et al, 2002;Li et al, 2007a;Liu et al, 2007). Given the crucial roles of Olig transcription factors, regulation of Olig gene expressions in post-injury GPCs could be considered a reasonable approach to promote the oligodendrogenesis after SCI.…”

Disc1 regulatesfoxd3andsox10expression, affecting neural crest migration and differentiation

“…In zebrafish, the specification of peripheral neurons relies on Sox10 function (Carney et al, 2006). Additionally, the formation of glial populations, both peripherally and centrally, is regulated by Sox10 across species (Dutton et al, 2001b;Li et al, 2007;Liu et al, 2007;Svaren and Meijer, 2008). Although our Disc1 morphants have fairly normal peripheral neuronal populations, there is a dramatic increase in the number of peripheral glia.…”

Individual axons regulate the myelinating potential of single oligodendrocytes in vivo

“…Here, we use zebrafish, which have recently become established as a powerful model for the study of glial cells and myelinated axons (Brosamle and Halpern, 2002;Buckley et al, 2010;Kazakova et al, 2006;Kirby et al, 2006;Li et al, 2007;Lyons et al, 2009;Monk et al, 2009;Pogoda et al, 2006;Takada and Appel, 2010), to study the role that axons play in regulating CNS myelination in vivo. As is the case in mammals, we show that single oligodendrocytes in zebrafish myelinate either a small number of large caliber axons or a larger number of smaller axons.…”