Altered Primary Somatosensory Neuron Development in a Pten Heterozygous Model for Autism Spectrum Disorder.

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interactions, repetitive behaviors, and hyper- or hyposensitivity to sensory stimuli. The cellular mechanisms underlying the emergence of abnormal sensory sensitivity in ASD are not fully understood. Recent studies in rodent models of ASD identified differences in dorsal root ganglia (DRG) neurons that convey somatosensory information to the central nervous system. However, it is unknown how ASD-associated alterations in DRG neurons emerge during development and if these phenotypes are conserved across ASD models. We examined Pten (phosphatase and tensin homolog) heterozygous mice (Pten) as a model for syndromic ASD and identified altered responses to sensory stimuli. Transcriptomic and in vivo analysis identified alterations in subtype-specific markers of DRG neurons in Ptenmice, emerging during early DRG development and involving dysregulation of signaling pathways downstream of PTEN. Finally, we show that mice harboring an ASD-associated mutation (Pten) show nearly identical alterations in the expression of somatosensory neuron subtype-specific markers. These results show that precise levels of PTEN are required for proper somatosensory development and provide insight into the molecular and cellular basis of sensory abnormalities in a model for syndromic ASD.