Abstract
The Sox2 transcription factor, encoded by a gene conserved in animal evolution, has become widely known because of its functional relevance for stem cells. In the developing nervous system, Sox2 is active in neural stem cells, and important for their self-renewal; differentiation to neurons and glia normally involves Sox2 downregulation. Recent evidence, however, identified specific types of fully differentiated neurons and glia that retain high Sox2 expression, and critically require Sox2 function, as revealed by functional studies in mouse and in other animals. Sox2 was found to control fundamental aspects of the biology of these cells, such as the development of correct neuronal connectivity. Sox2 downstream target genes identified within these cell types provide molecular mechanisms for cell-type-specific Sox2 neuronal and glial functions. SOX2 mutations in humans lead to a spectrum of nervous system defects, involving vision, movement control, and cognition; the identification of neurons and glia requiring Sox2 function, and the investigation of Sox2 roles and molecular targets within them, represents a novel perspective for the understanding of the pathogenesis of these defects.
Highlights
Sox2 is expressed in the primordium of the cerebellum, and, postnatally, it is maintained in the Bergmann glia (BG), a unipolar cell type with the soma in the Purkinje cell (PC) layer and their radial processes going through the molecular layer and reaching the pia [40] (Figure 1A)
Müller glia (MG) maintains neurogenic capacity in the adult retina, and it has been shown to be able to re-enter the cell cycle in response to retinal injury [55,56]. These findings indicate that Sox2 may retain some of its stem cell-related functions, acting within subpopulations of differentiated glia, as they occasionally resume stem cell character
The identification of functional roles for Sox2 in specific types of differentiated neurons and glia opens a new perspective in the understanding of the function of this transcription factor in neural development and disease, enlarging Sox2 functional roles beyond those it plays within stem cells
Summary
The transcription factor Sox has become widely known because of its functional connection to the stem cell state (reviewed in references [1,2,3,4]). Sox is expressed, and required, from the earliest stages of embryonic development in the pluripotent stem cells of the blastocyst inner cell mass; its knock-out in mouse causes early embryonic lethality [5]. Sox is highly expressed in neural stem/precursor cells, constituting the ventricular zone of the developing neural tube and, in general, it is downregulated in differentiating cells as they progressively move out of the ventricular zone into the outer layers of the neural tube. Sox conditional deletion in the developing neural tube impacts neural stem cell (NSC) function, both in vitro and in vivo [2,8,9]. Sox was found to be absolutely required for the development of the mouse olfactory neuroepithelium [9,10], a neurogenic epithelium containing Sox2-positive, long-term self-renewing stem-like cells [11]
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