THE WNT/B-CATENIN SIGNALING PATHWAY REGULATES SOX2 EXPRESSION AND NEUROGENESIS DURING OLFACTORY REGENERATION IN XENOPUS TADPOLES

PAZ, DANTE; POZZI, ANDREA; FRONTERA, JIMENA

Rio de Janeiro

Congreso; IBRO - 9th World Congress International Brain Research Organization; 2015

International Brain Research Organization

The olfactory epithelium (OE) is a pseudo stratified epithelium composed of olfactory receptor neurons (ORNs), sustentacular (SUS) cells and basal cells (BCs). The ability of the OE to regenerate after injury is mediated by at least two populations of presumed stem cells: globose (GBCs) and horizontal basal cells (HBCs). Of these two populations of neural stem cells, GBCs are moleculary and phenotipically analogous to the olfactory progenitors of the embryonic placode. In contrast, HBCs are a reserve stem cell population that appears later in development and requires activation by severe epithelial damage before contributing the epithelial reconstitution. Neither HBC emergence nor the mechanisms of activation after injury are well understood.Our work has focused on the analysis of the factors and mechanisms involved in homeostasis and neural regenerative capacity of the Xenopus laevis tadpoles OE. We studied the regeneration dynamics of the different cell types after chemical injury of the OE, and the implication of the transcription factor Sox2 and its regulation through the Wnt signaling pathways. Our results demonstrate Sox2 expression in proliferating basal cells found near to the basement membrane, some of which were identified as immature neurons expressing GAP43. This suggests that neural progenitors in the basal layer of the OE express the transcription factor Sox2, and the expression of this protein is maintained until the early stages of neuronal differentiation.During regeneration of the OE after chemical destruction by Zinc sulphate treatment, we have determined an increase of gene expression of Sox2 and increased Sox2 positive (Sox2+) basal cells with proliferative potential therefore suggest that basal cells are Sox2 expressing neural progenitors and would contribute to the replenishment of olfactory cells.To evaluate the implication of the Wnt signaling pathway in regulation of Sox2 expression, inhibition of Wnt/β-catenin pathway was induced by Norcantharidin. Under the canonical Wnt pathway inhibition, we observed a marked decrease in the Sox2 gene expression as well as the number of Sox2+ basal cells during regeneration. However, no direct effect on Sox2 was observed under normal conditions. These results suggest that Wnt/β-catenin signaling pathway would be involved in the regulation of Sox2 expression mainly under massive regeneration conditions.Taken together, our results indicate that activation of theWnt/β-catenin signaling pathway is required for Sox2 expression in olfactory neural precursors after a massive destruction of the OE. This pathway may be related with the HBCs activation. However, under normal physiological conditions, other factors would be involved and responsible for the regulation of Sox2 in basal cells.