Sox8 is a transcription factor that belongs to the Sox family of high-mobility-group domain containing proteins and is closely related to Sox9 and Sox10. During prenatal development, Sox8 is expressed in several ectoderm-, endoderm- and mesoderm-derived tissues and has been implicated in processes of organogenesis and differentiation. Sox8 expression is found in several important cells such as Sertoli cells in the male gonad, glial cells, satellite cells, and chondrocytes. However, Sox8 is not essential for the proper development of any of the involved systems, as it functions redundantly with Sox9 or Sox10 and no major developmental disturbances have been noticed in its absence. Despite its perceived limited importance as a developmental regulator, Sox8 exhibits a more significant role in late development and adult tissues. Several studies highlight the importance of Sox8 for the homeostasis of adipose tissue, Sertoli cells and the blood-testis-barrier functioning, and the maintenance of myelin in the central nervous system. Emerging evidence points to SOX8 as a promising candidate for a disease-causing gene in humans and suggests that changes in SOX8 function or expression could contribute to pathological states. For instance, genetic variants of SOX8 have been linked to multiple sclerosis and familial essential tremor, while SOX8 alterations have been related to poor cancer prognosis and infertility. This Review provides an overview of Sox8's versatile role in development and adult tissues as well as its lesser-known contributions to various diseases, and its potential as a therapeutic target.

Oligodendroglial cells generate myelin sheaths in the vertebrate central nervous system to render rapid saltatory conduction possible and express the highly related Sox8, Sox9 and Sox10 transcription factors. While Sox9 and Sox10 fulfill crucial regulatory roles, Sox8 has only a limited impact on oligodendroglial development and myelination. By replacing Sox10 with Sox8 or Sox9 in the oligodendroglial Oln93 cell line, and comparing the expression profiles, we show here that Sox8 regulates the same processes as Sox10 and Sox9, but exhibits a substantially lower transcriptional activity under standard culture conditions. Sox8 influences fewer genes in their expression and changes their expression level less drastically, despite comparable binding to relevant regulatory regions in oligodendroglial cells. Therefore, it is likely that Sox8 and Sox10 vary in their transcriptional activity because of differences in their interactions with partner proteins. Intriguingly, it is the aminoterminal one third of the Sox protein that is responsible for the differential activities of Sox8 and Sox10, rather than the carboxyterminal two thirds that contain the known transactivation domains. Our study aims to provide an understanding of the relationship of Sox8 and Sox10 as paralogous transcription factors and their degree of functional redundancy in oligodendroglial cells, along with implications for health and disease.