Abstract
The expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.
Highlights
The proper function of the cerebral cortex requires the formation of highly stereotyped circuits during development
Foxp2 expression is enriched in developing corticothalamic projection neurons
Initial Foxp2 expression mapping studies determined that Foxp2 transcript and protein expression begin prenatally, with the onset of protein expression delayed relative to the mRNA, and with protein present primarily in postmitotic neurons (Ferland et al, 2003)
Summary
The proper function of the cerebral cortex requires the formation of highly stereotyped circuits during development These circuits are built through interdependent processes, including proliferation of neural progenitors, migration of neurons to their appropriate positions, morphological and physiological differentiation of diverse neuron subtypes, and the formation of synapses of requisite strength between appropriate pairs of neurons. Impairments in these fundamental aspects of development can lead to lifelong dysfunction of the cortex, which is believed to contribute to core symptoms of many neurodevelopmental disorders (Rubenstein and Rakic, 2013). Human neuroimaging and animal studies have identified alterations in basal ganglia function that could contribute to the clinical disorder symptoms (Vargha-Khadem et al, 1998; Belton et al, 2003; Groszer et al, 2008; French et al, 2012; Chen et al, 2016), but whether changes in cerebral cortical organization and function are critically involved in impairments associated with FOXP2 mutations is currently unknown
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