Foxp2 regulates neuronal differentiation and neuronal subtype specification

Abstract

Mutations of the transcription factor FOXP2 in humans cause a severe speech and language disorder. Disruption of Foxp2 in songbirds or mice also leads to deficits in song learning or ultrasonic vocalization, respectively. These data suggest that Foxp2 plays important roles in the developing nervous system. However, the mechanism of Foxp2 in regulating neural development remains elusive. In the current study, we found that Foxp2 increased neuronal differentiation without affecting cell proliferation and cell survival in primary neural progenitors from embryonic forebrains. Foxp2 induced the expression of platelet-derived growth factor receptor α, which mediated the neurognic effect of Foxp2. In addition, Foxp2 positively regulated the differentiation of medium spiny neurons derived from the lateral ganglionic eminence and negatively regulated the formation of interneurons derived from dorsal medial ganglionic eminence by interacting with the Sonic hedgehog pathway. Taken together, our results suggest that Foxp2 regulates multiple aspects of neuronal development in the embryonic forebrain.

FoxP2 protein levels regulate cell morphology changes and migration patterns in the vertebrate developing telencephalon

“…Clovis et al (2012) described a delay in neurite outgrowth that impairs radial migration of cortical projections neurons after ectopic expression of FoxP2. In contrast, other works report that overexpression of FoxP2 leads to neurite elongation (Vernes et al 2011;Chiu et al 2014). The role of FoxP2 in cell morphology continues to be ill known.…”

“…FoxP2 also expresses in the mouse cerebral cortex from stage E14.5 (Ferland et al 2003;Tsui et al 2013). The function of FoxP2 has been analyzed during development of the central nervous system (Clovis et al 2012;Rousso et al 2012;Tsui et al 2013;Chiu et al 2014). FoxP2 knocked down cortical precursors do not transition from radial glia to intermediate precursors (Tsui et al 2013).…”

Physiological Signatures of Dual Embryonic Origins in Mouse Skull Vault

“…However, higher levels of expressions of GRIAL1, SGOL1 and Igfbp6 were found within parietal bone that displayed anti-proliferative feature, such as overexpression of GRIAL1 is anti-proliferative [28], and SGOL1 and Igfbp6 are involved in cell apoptosis [29-31]. Foxp2 can increase cell differentiation without affecting cell proliferation and cell survival [32], and transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint [33]. Our findings are consistent with the publication that osteoblasts from the neural crest-derived frontal bone are less differentiated, grow faster compared to parietal bone-derived osteoblasts [3].…”

What can mice tell us about Foxp2 function?

“…Several papers have described early developmental roles for Foxp2 in the embryonic forebrain [48,49] and spinal cord [50 ]. Given that expression persists into adulthood [19 ], it seems likely that the protein also has regulatory functions in postnatal animals, perhaps throughout adult life.…”