Abstract
The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.
Highlights
The development of multicellular organisms and the maintenance of homeostasis in adulthood are achieved by complex control of basic cellular processes such as the maintenance of pluripotent stem cells, cell fate decision, differentiation, proliferation, and cell death
We demonstrate that transition from proliferation to retinoic acid (RA) induced neural differentiation of NT2/D1 cells coincides with complete OCT4 down-regulation (Stevanovicet al., 2017)
We demonstrated that increase in SOX2 and SOX3 protein expression is β-catenin dependent, while overexpression of SOX1 is governed by β-catenin-independent manner (Figure 5B) (Mojsin et al, 2015)
Summary
The development of multicellular organisms and the maintenance of homeostasis in adulthood are achieved by complex control of basic cellular processes such as the maintenance of pluripotent stem cells, cell fate decision, differentiation, proliferation, and cell death. Through a cooperative interaction these factors drive pluripotent-specific expression of the numerous genes and play key roles in determining the fate of ESCs, regulating two distinct and opposing functions: self-renewal and differentiation (Figure 1) The authors reveal that sequentially acting SOX TFs coordinate neural gene expression from pluripotent cells to later stages of neuronal development.
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