The neuronal co-repressor CoREST: An additional marker for immature neurons within the olfactory epithelium of the developing and adult mouse

摘要

In a previous study we have identified the mouse homologue of human Co-REST, a co-repressor to the zinc finger transcriptional repressor REST (repressor element-1 silencing transcription factor) and have determined its spatio-temporal expression pattern in the developing and newborn mouse brain (1). We have shown that CoREST is present in the developing neural tissue and persists in neurogenic areas throughout adulthood. Co-REST not only mediates the transcriptional repression of REST target genes, but also exerts REST-independent functions. CoREST target genes were found to be involved in pluripotency networks, neural stem cell differentiation, early neural fate decisions, and neuronal subtype specification (2). In this project we have been focussing on the stage -specific expression of Co-REST in the mammalian olfactory epithelium (OE), which is known to harbour a pool of highly dynamic neurogenic cells (neural stem/precursor cells, NSCs/NPCs). Using immunohistochemistry we have determined the spatio-temporal expression pattern of Co-REST in the developing and adult mouse OE. Co-expression studies have been performed using antibodies against stem cell-related transcription factors, NPC-associated cytoplasmic proteins, and neuron-specific terminal differentiation markers. Here we have shown that the stem cell-associated proteins Sox2 and Nestin are co-localized in the young OE, showing prominent staining in basal and apical regions. Interestingly, expression of Co-REST is detectable exclusively in Sox2/Nestin-free areas. From mid-gestation on, CoREST expression appears restricted to Doublecortin (Dcx) and GAP43-containing neuronal precursors. CoREST does not seem to colocalize with the olfactory marker protein (OMP), a marker being only expressed in mature olfactory receptor neurons (ORNs). Based on these results we conclude that CoREST is not responsible for stem cell-related gene repression, but is rather involved in a mechanism keeping ORNs in a precursor state. References: (1) Tontsch S, Zach O, Bauer HC (2001) Mech Dev. 108(1-2):165-9. (2) Abrajano JJ, Qureshi IA, Gokhan S, Molero AE, Zheng D, Bergman A, Mehler MF (2010). Proc Natl Acad Sci U S A. 107(38):16685-90. (2) Supported by grants from the Paracelsus Medical University (PMU, Salzburg, Project R-10/05/022-LEH) and by NEUROBID (EU 7th FP).