FOXP2 (Forkhead bOX 2) is the first gene implicated in speech and language and was initially characterized through investigations in a large pedigree called the KE family. It is located on human chromosome 7q31 and encodes a protein of 715 amino acids. The speech and language problems (i.e., developmental verbal dyspraxia – DVD) observed in the KE family occur due to the R553H missense mutation, which produces an arginine to histidine substitution in the DNA binding domain of the FOXP2 protein. Interestingly, disruption of Foxp2 in songbirds and mice has been found to cause inaccurate vocal imitation and impaired ultrasonic vocalization, respectively. Numerous studies have also demonstrated the importance of Foxp2 in neural development and synaptic plasticity. For example, R552H heterozygous mice display abnormal synaptic plasticity in striatal and cerebellar neural circuits. Implications of the Foxp subfamily in neural development include, among others, the role of Foxp1 in promoting midbrain identity in vitro and the role of Foxp2 in controlling neurogenesis during embryonic cortical development. However, the mechanism underlying these physiological functions remains unclear. Chiu and colleagues in their article provide striking evidence supporting a prominent role of Foxp2 in neuronal development of the embryonic forebrain. Chiu and colleagues (2014) used neural progenitor cells isolated from the forebrain of E14.5 mouse embryos to study these roles of Foxp2. To test whether Foxp2 promotes neuronal differentiation, the authors performed gain-of-function experiments with cerebral cortex (CTX) progenitors (since Foxp2 expression is low in the CTX) and loss-of-function experiments with ganglionic eminence progenitors (GE) (as ...... half of the article ......d if they are also negatively regulated by Foxp2 in order to provide an overview of the role of Foxp2 in MGE Foxp2 inhibits the Shh pathway in MGE, thereby suppressing MGE-derived interneurons. This raises the question of how Foxp2 inhibits Shh since the authors demonstrated no interaction between Foxp2 and NKX2-1 (induced by Shh), a crucial transcription factor required. for the generation of MGE-derived neurons. Even more interesting, this study provides a new perspective for the generation of MGE-derived neurons pathogenesis of schizophrenia since interneuronal deficits have been found in schizophrenic patients; thus, disruption of Foxp2 could be responsible for these deficits and consequently responsible for this neuropsychiatric disorder.
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