The differentiation of glial precursors into neuronal-like cells through the Wnt and Neurotrophin signaling pathways via Ctnnβ1.

Abstract

Glial precursor cells are among the major types of glia in the dorsal root ganglias (DRGs) of the peripheral nervous system. Previous studies have shown that the transdifferentiation of DRGs-derived glial precursor cells contributes to peripheral neurogenesis. In the present study, we investigated the mRNA expression profiles and examined the effects of differential expression mRNAs (DEMs) during the differentiation of glial precursor cells derived from the rat DRGs. We characterized glial precursor cells derived from rat DRGs explants using immunofluorescence. Sequencing was subsequently conducted, followed by enrichment analysis utilizing gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The identified genes were subsequently subjected to protein-protein interaction (PPI) network analysis during the differentiation process of glial precursor cells derived from the rat DRGs. The establishment of a sciatic nerve injury (SNI) model was followed by the detection of the expression of key genes in the Wnt and Neurotrophin pathways in the DRGs of SNI rats via qRT-PCR. Additionally, the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was employed to assess apoptosis in the DRGs. We detected the mRNA expression profiles during the neuronal differentiation of rat DRGs-derived glial precursor cells. More DEMs and GO terms were detected on the third day of DRGs-derived glial precursor cells transdifferentiation, accompanied by morphological alterations in the cells; that is, some cells presented neuronal-like phenotypic characteristics (the early neuronal marker Tuj1 was positive). KEGG enrichment and PPI network analyses revealed that Wnt and Neurotrophin pathways play crucial roles in the process of glial precursor cell differentiation into neuronal-like cells. After knocking down cadherin-associated protein beta 1 (Ctnnβ1) in the SNI model, the number of apoptotic cells was significantly reduced, and the expression of Wnt4 and Ntrk3 was significantly increased. The Ctnnβ1 gene may be a crosstalk factor between the Wnt and Neurotrophin pathways that negatively regulates the differentiation of glial precursor cells.