title: FoxP2 regulates neurogenesis during embryonic cortical development.
abstract: The transcription factor FoxP2 has been associated with the development of human speech but the underlying cellular function of FoxP2 is still unclear. Here we provide evidence that FoxP2 regulates genesis of some intermediate progenitors and neurons in the mammalian cortex, one of the key centers for human speech. Specifically, knockdown of FoxP2 in embryonic cortical precursors inhibits neurogenesis, at least in part by inhibiting the transition from radial glial precursors to neurogenic intermediate progenitors. Moreover, overexpression of human, but not mouse, FoxP2 enhances the genesis of intermediate progenitors and neurons. In contrast, expression of a human FoxP2 mutant that causes vocalization deficits decreases neurogenesis, suggesting that in the murine system human FoxP2 acts as a gain-of-function protein, while a human FoxP2 mutant acts as a dominant-inhibitory protein. These results support the idea that FoxP2 regulates the transition from neural precursors to transit-amplifying progenitors and ultimately neurons, and shed light upon the molecular changes that might contribute to evolution of the mammalian cortex.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada M5G 1L7.
authors.forename: David
authors.initials: D
authors.lastname: Tsui
authors.forename: John P
authors.initials: JP
authors.lastname: Vessey
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomita
authors.forename: David R
authors.initials: DR
authors.lastname: Kaplan
authors.forename: Freda D
authors.initials: FD
authors.lastname: Miller
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins