Neuronal TDP-43 regulates myelin formation via neurexin 1 mRNA stabilization

TAR DNA-binding protein 43 (TDP-43) is a major pathological protein inextricably linked to Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Hypomyelination was detected in neuronal- specific TDP-43 knockout (TDP-43cKO) mice, and this impairment was recovered by the supplementation of cytoplasmic TDP-43 in neurons. We herein investigated the mechanisms that neuronal TDP-43 regulating neuron-oligodendrocyte interactions using the TDP-43cKO mice. Overall design: AAV-FLEX-GFP or AAV-FLEX-TDP-43mNLS-GFP was injected into the hippocampus of TDP-43cKO or control (CamKIIcre/-) mice. GFP-positive cells were sorted from brain suspensions pooled from 3-4 animals in each group by FACS. RNAs were extracted from the isolated cells and applied for RNA-seq. We then performed gene profiling analysis using data obtained from RNA-seq of AAV-FLEX-GFP injected control moue (NC-GFP), AAV-FLEX-GFP injected TDP-43cKO mouse (TDP-43cKO-GFP) and AAV-FLEX-TDP-43mNLS-GFP injected TDP-43cKO mouse (TDP-43cKO-TDP-43mNLS).