Differential and Overlapping Pattern of Foxp1 and Foxp2 Expression in the Striatum of Adult Mouse Brain

Genetic mutations of FOXP1 and FOXP2 are associated with neurodevelopmental diseases. It is important to characterize the cell types that express Foxp1 and Foxp2 in the brain. Foxp1 and Foxp2 are expressed at high levels in the striatum of mouse brains. There are two populations of striatal projection neurons (SPNs), dopamine D1 receptor (D1R)-expressing striatonigral neurons and D2 receptor (D2R)-expressing striatopallidal neurons. In addition to SPNs, there are different types of striatal interneurons. Here, we quantitatively analyze the expression pattern of Foxp1 and Foxp2 with respect to specific cell types of projection neurons and interneurons in the striatum of adult mouse brains. Double immunostaining and in situ hybridization showed that Foxp1 and Foxp2 were specifically expressed in SPNs, but not in interneurons. For Foxp1, 50-57% of Foxp1-positive neurons co-expressed D1R mRNA, and 45-52% of Foxp1-positive neurons co-expressed D2R mRNA in the striatum at rostrocaudal levels. For Foxp2, 65-77% of Foxp2-positive neurons co-expressed D1R mRNA, and 21-26% of Foxp2-positive neurons co-expressed D2R mRNA in the striatum at rostrocaudal levels. Neither Foxp1 nor Foxp2 was found to co-localize with parvalbumin, somatostatin, nNOS, calretinin and ChAT in interneurons of the striatum. Moreover, none of parvalbumin-, somatostatin-, nNOS-, and calretinin-positive interneurons co-expressed Foxp1 or Foxp2 in the cerebral cortex. As Foxp1 and Foxp2 can form heterodimers for transcriptional regulation, the differential and overlapping expression pattern of Foxp1 and Foxp2 in SPNs implicates coordinate and distinct roles of Foxp1 and Foxp2 in developmental construction and physiologic functions of striatal circuits in the brain.