Neuronal CTGF/CCN2 negatively regulates myelination in a mouse model of tuberous sclerosis complex.

ABSTRACT: Disruption of myelination during development has been implicated in a range of neurodevelopmental disorders including tuberous sclerosis complex (TSC). TSC patients with autism display impairments in white matter integrity. Similarly, mice lacking neuronal Tsc1 have a hypomyelination phenotype. However, the mechanisms that underlie these phenotypes remain unknown. In this study, we demonstrate that neuronal TSC1/2 orchestrates a program of oligodendrocyte maturation through the regulated secretion of connective tissue growth factor (CTGF). We characterize oligodendrocyte maturation both in vitro and in vivo. We find that neuron-specific Tsc1 deletion results in an increase in CTGF secretion that non-cell autonomously stunts oligodendrocyte development and decreases the total

SUBMITTER: Ercan E 

PROVIDER: S-EPMC5339668 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature