FOXP2 NEURAL NETWORK · A tangled web: Foxp2 and language related neural networks

FOXP2 was the first gene directly implicated in language development and mutations cause rare but severe forms of language disorder. FOXP2 encodes a protein that acts as a transcription factor, regulating the expression of other genes. Our previous work used FOXP2 as an entrypoint to define molecular networks associated with language, and showed that Foxp2 contributes to neurite outgrowth in the developing brain. Furthermore, mouse models suggest that Foxp2 may be acting in language related areas of the brain to affect connectivity and plasticity. Here, we aim to understand fundamental aspects of neural network formation and neuronal activity controlled by Foxp2. We will use a model system (the mouse brain) to investigate how neuronal network connectivity develops in language related brain areas. We will also manipulate levels of Foxp2 and its previously identified target genes to understand how these genes contribute to network formation. We will define the upstream regions and factors that regulate Foxp2 expression to better understand the wider molecular networks associated with language development. We predict that FOXP2 expressing neurons are related to language circuitry and thus we will use the enhancer regions that we identify to generate mouse lines that will mark out specific sub-populations of Foxp2 positive neurons in the developing brain, to shed light on the connections they form. Lastly, we will use these enhancer regions to create mouse lines that allow us to observe the activation of Foxp2 positive neurons and the role of these circuits during behavioural tasks. Taken together, this work will help us to understand the formation and activity of language related neural networks, and shed light on underlying cellular and network defects that may be associated with language disorders.