Neuronal expression of SOX2 is enriched in specific hypothalamic cell groups

Abstract

The transcription factor SOX2 has many established roles in neural development but is generally considered to have limited activity in the adult brain. As part of a study of neuronal phenotypes in the adult rodent hypothalamus, we have now used immunohistochemical analysis to investigate the expression of SOX2 in the adult rat and mouse hypothalamus. Our analysis has revealed that SOX2 protein is extensively expressed in cells of the suprachiasmatic nucleus (SCN). Co-localization with the nuclear marker proteins NeuN and MeCP2 confirmed SOX2 expression in mature neurons of the rat SCN, and the functional integrity of these SOX2+ neurons was also confirmed by demonstrating co-localization with light-induced EGR1 protein. In addition to the SCN, we have also revealed a population of SOX2+/(NeuN+/MeCP2+) neurons in the rat periventricular nucleus (PeN). However, in other hypothalamic nuclei such as the supraoptic nucleus (SON) SOX2+ cells were rare. In extra-hypothalamic areas, SOX2+ cells were also scarce although we have confirmed populations of non-neuronal SOX2+ cells in both the rat sub-ventricular zone (SVZ) and sub-granular zone (SGZ) of the hippocampus. In addition, we have identified an extensive, novel population of non-neuronal SOX2+ cells in the rat subfornical organ (SFO). Our findings provide further evidence of 'immature' phenotypes in rodent SCN neurons and, given the extensive expression of SOX2 across these hypothalamic neurons, may identify a common regulatory factor that maintains this unusual neuronal phenotype. Conservation of SCN SOX2 expression in both rat and mouse indicates a functional requirement for this transcription factor that may be integral to the role of these SCN neurons in mediating daily physiological rhythms.

Keywords: Hypothalamus; Periventricular nucleus; Sox2; Subfornical organ; Suprachiasmatic nucleus; Transcription factor.