Sociability and synapse subtype-specific defects in mice lacking SRPX2, a language-associated gene

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The transcription factor FoxP2 is linked to developmental brain disorders affecting language.
• The precise mechanisms by which FoxP2 influences neural circuitry development are not fully understood.
• Mutations in SRPX2, a FoxP2 target gene, are associated with human language deficits.

Purpose of the Study:

• To characterize the function of the sushi domain protein SRPX2 in neural development.
• To investigate the role of SRPX2 in regulating neural circuitry, communication, and social behaviors.
• To elucidate the contribution of SRPX2 to FoxP2-mediated regulation of vocalization and social circuits.

Main Methods:

• Generation and analysis of mice lacking the SRPX2 gene (SRPX2 knockout).
• Assessment of excitatory and inhibitory synapse density in the cerebral cortex using VGlut1 and VGlut2 markers.
• Evaluation of ultrasonic vocalization patterns in neonatal pups and social novelty preference in adult mice.

Main Results:

• SRPX2 knockout mice exhibit a specific reduction in excitatory VGlut2 synapses in the cerebral cortex.
• VGlut1 and inhibitory synapses remained largely unaffected in SRPX2 knockout mice.
• SRPX2 knockout mice displayed abnormal ultrasonic vocalization ontogeny and reduced preference for social novelty.

Conclusions:

• SRPX2 plays a critical functional role during brain development.
• The study implicates FoxP2 and its target SRPX2 in the development of vocalization and social circuits.
• Defects in SRPX2 are linked to alterations in neural circuitry, communication, and social behaviors.