Altered primary somatosensory neuron development in a Pten heterozygous model for autism spectrum disorder

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 mechanisms underlying the emergence of sensory features in ASD are not fully understood, but recent studies in rodent models highlight that these may result from differences in primary sensory neurons themselves. We examined sensory behaviors in a Pten haploinsufficient mouse model (PtenHet) for syndromic ASD and identified elevated responses to mechanical stimuli and a higher threshold to thermal responses. Transcriptomic and in vivo anatomical analysis identified alterations in subtype-specific markers of primary somatosensory neurons in PtenHet dorsal root ganglia (DRG). These defects emerge early during DRG development and involve dysregulation of multiple signaling pathways downstream of Pten. Finally, we show that mice harboring an ASD-associated mutation (PtenY69H) also show altered expression of somatosensory neuron subtype-specific markers. Together, 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.