Understanding the Conserved and Species-Specific Functions of FOXP2, a Gene Implicated in Speech and Language Development




Hickey, Stephanie Lepp

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During my dissertation work I sought to better understand the conserved and human-specific functions of FoxP2. Intrigued by the enrichment of FOXP2 in the human subplate layer, I hypothesized that FOXP2 regulates evolutionarily distinct subplate gene expression patterns and tested this theory by performing RNA-seq in human differentiating neurons and leveraging publically available developmental expression data from human, macaque, and mouse cortex in order to identify human specific, primate specific, and conserved subplate genes regulated by FOXP2. This study not only identified human specific targets in this expanded, transient region, but it may also inspire research of the conserved, non-cell-autonomous role of FoxP2 in the maturation of thalamocortical circuitry. Additionally, I performed ChIP-seq and RNA-seq in human neural progenitor cells and found evidence that FOXP2 may actively modify the chromatin landscape. This lead me to hypothesize that by modifying the chromatin landscape of neural progenitors FOXP2 turns off cellular programs that maintain an undifferentiated state while turning on programs that drive a cell towards a neuronal fate. To test this hypothesis, I identified areas of nucleosomal depletion using ATAC-seq and correlated epigenetic changes caused by FOXP2 expression to changes in gene expression in proliferating and differentiating human neurons. This allowed me to define two separate molecular mechanisms by which FOXP2 regulates gene expression in human neurons, even finding a potential FOXP2 co-activator. Together, these studies push forward our understanding of the function of FoxP2, especially in human neurons, and provide a source of data from which the next hypotheses concerning FoxP2 and human language formation may be derived.

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