Approximately, 1 in 59 children in the United States are affected with autism spectrum disorder (ASD). Numerous studies have identified mutations in FOXP1, a gene encoding a transcription factor enriched in the developing and mature neocortex, as causal for ASD. Our group has previously shown that loss of Foxp1 in the mouse cortex leads to reduced cortex size, alterations in cortical lamination, and changes in relative thickness of cortical layers. However, the mechanisms underlying these changes remain unclear. I propose to characterize the developmental requirement of neocortical Foxp1 using time point specific conditional knock-outs of Foxp1 and by measuring transcriptional targets using single nuclei RNA sequencing. I hypothesize that during early embryonic development, Foxp1 facilitates the development of deep layer neurons by repressing factors that specify upper layer neuronal fate. In contrast, I hypothesize that Foxp1 is critical for neuronal identity during late cortical development. The outcome of this work will allow for a better understanding of how Foxp1 governs early cortical development and potential therapeutic windows and molecular pathways for ameliorating loss of function Foxp1 mutations.
Cortical development is a tightly controlled process and any deviation may increase the susceptibility to neurodevelopmental disorders. Greater knowledge of how specific genes functionally regulate cortical development will improve the opportunities for therapeutic interventions. FOXP1 is a transcription factor associated with neurodevelopmental disorders and cortical development, and thus understanding the molecular pathways regulated by FOXP1 during brain development will provide entry points for novel therapies related to brain disorders.
