Functional characterization of the transcription factor FOXP1 and its target genes in cognitive development

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Speech and language disorders are characterized by an impaired acquisition of fluent, comprehensible language and sometimes co-segregate with other developmental disorders such as intellectual disability. Intellectual disability is a widespread developmental disorder characterized by limitations in intellectual abilities (IQ <70). For many patients, both language disorders and intellectual disability are caused by genetic defects. The first and best known gene associated with language disorders is the Forkhead Box P2 (F0XP2) gene. F0XP2 is one of four members of the FOXP ¬-subfamily of forkhead box transcription factors. In a recent study, we identified deletions of the related FOXP1 gene In three patients with intellectual disability and significant impairment of speech and language abilities. This finding indicated that the transcription factor FOXP1, very similar to FOXP2, might play an important role during brain development. Unlike F0XP2, very little is known about how F0XP1 regulates these processes. The goal of our project is to characterize the role of F0XP1 in brain development and to identify the genes that represent the downstream targets of this protein in neuronal differentiation. Our main aims are to generate a conditional Foxp1 knockout mouse, where Foxp1 is deleted specifically in the central nervous system, to sidestep the embryonic lethality of Foxp1 conventional knockout mice at embryonic day (E) 14.5 due to heart defects. We will use this conditional knockout to investigate brain development in the absence of Foxp1 and to identify targets of Foxp1.