Dynamics of cortical progenitors and production of subcerebral neurons are altered in embryos of a maternal inflammation model for autism.

The broad impairments in cognitive and neurologic functioning found in Autism Spectrum Disorder (ASD) patients are thought to originate during early prenatal developmental stages. Indeed, postmortem and imaging studies in ASD patients detected white-matter abnormalities, as well as prefrontal and temporal cortex deficits, evident from early childhood. Here, we used Maternal Immune Activation (MIA), a mouse model for ASD, in which the offsprings exhibit Autistic-like behaviors as well as cortical abnormalities. However, the dynamics that influence the number and the identity of newly born cortical neurons following maternal inflammation remains unknown. Our study shows early changes in the duration of the S-phase of PAX6+ progenitors, leading to an increased proportion of neurogenic divisions and a reciprocal decrease in the proliferative divisions. In two different time points of maternal inflammation, MIA resulted in an overproduction of CTIP2+ cortical neurons, which remained overrepresented at the end of gestation and in postnatal mice. Interestingly, MIA-resistant IL6-KO mice did not exhibit these changes. Lastly, we propose that elevated levels of the transcription factor PAX6 following MIA supports the overproduction of CTIP2+ neurons. Taken together, our data reveals a possible link between maternal immune activation and the excess of cortical neurons found in the cortex of ASD patients.