[Poster] Dysregulation of the Wnt/β-Catenin signaling pathway via Rnf146 upregulation in a VPA-induced omuse model of autism spectrum disorder

This poster presents an investigation into the molecular mechanisms underlying autism spectrum disorder (ASD) using a valproic acid (VPA)-induced mouse model. The study focuses on Rnf146, a key regulator of the Wnt/β-catenin signaling pathway, and its role in ASD-like behavioral and synaptic deficits.

Using high-resolution proteomic analysis, the researchers identified 941 differentially expressed proteins in the prefrontal cortex of VPA-exposed mice, many of which overlapped with known ASD and developmental disorder risk genes. The findings revealed that Rnf146 upregulation perturbed the Wnt/β-catenin signaling pathway by promoting the degradation of Axin, a critical component of the pathway, leading to reduced levels of phosphorylated β-catenin.

Behavioral experiments demonstrated significant social impairments in VPA-exposed mice, which were further replicated in Rnf146-overexpressing mice. Electrophysiological studies showed that Rnf146 overexpression in the prefrontal cortex enhanced excitatory synaptic transmission, while RNA sequencing and functional analyses revealed upregulation of genes associated with synaptic functions and the Wnt signaling pathway.

This study provides valuable insights into the molecular underpinnings of ASD and proposes the Rnf146-Wnt/β-catenin axis as a potential target for therapeutic interventions to address ASD-related social deficits and synaptic imbalances.