FOXP genes, neural development, speech and language disorders

Abstract

Foxp subfamily genes were recently recognized to be members of the Fox gene family. Foxp subfamily members contain a zinc finger domain and a leucine zipper motif in addition to a forkhead domain and their DNA binding capacities and transcriptional activities are regulated by homo- and heterodimerization via a zinc finger and a leucine zipper motif. Three Foxp subfamily members are abundantly expressed in developing brains. The expression patterns of these genes are overlapping, but they are distinctly expressed in some regions. Thus these genes appear to be involved in the development control of the central nervous system. Recently, FOXP2, a member of the Foxp subfamily, was identified as the first gene to be linked to an inherited form of language and speech disorder. The discovery of a mutation in FOXP2 in a family with a speech and language disorder opened a new window to understanding the genetic cascades and neural circuits that underlie speech and language via molecular approaches. The spatiotemporal FOXP2 mRNA expression pattern suggests that the basic neural network that underlies speech and language may include motor-related circuits, including frontostriatal and/or frontocerebellar circuits. This assumption is supported by brain imaging data obtained by using fMRI and PET on the FOXP2-mutated patients and also by analysis of Foxp2 mutant mice.