Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval.

The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared with female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared with females and a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals. We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls.