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Relevance of the Interaction between FoxP1, FoxP2 and FoxP4 for vocal learning / vocal reproduction in birds

Dr. Ezequiel Mendoza

In 2001 the chase for genes associated with speech resulted in the identification of a mutation in FOXP2 in individuals that share severe and characteristic core deficits of receptive and productive language. The analysis of the molecular role of FoxP2 in learned vocalizations, has recently been significantly advanced using songbirds as a model [1]. It was demonstrated that FoxP2 pattern of expression in birds vocal learners differ from vocal- non learners, specially in Area X, a part of the specialized basal ganglia forebrain network required for vocal learning that vocal non- learners do not possess. Moreover, FoxP2 expression is elevated in Area X at the time both, when young zebra finches learn to imitate an adult model song and at the time when adult canaries remodel their songs seasonally [2].

The Fox family is composed of over 20 different members, all of which contain a winged-helix motif that is responsible for DNA binding activity. In mice there is co-expression of Foxp2, with Foxp1 and Foxp4, in brain, gut and pulmonary tissues [3]. In vitro, it has been demonstrated that FoxP2 must dimerize either with itself, with FoxP1 or FoxP4, for transcriptional repression to occur and that the leucine zipper is important for dimerization [4]. In my PhD project I am investigating the cellular and behavioral relevance of these interactions in vivo, focusing on brain regions in zebra finches where co-expression occurs.


(1) Scharff C. And Haesler S. (2005) An evolutionary perspective on FoxP2: strictly for the birds? J. Neurosci., 25(36):8250-8. (2) Haesler S., Wada K., Nshdejan A., Morrisey E.E., Lints T., Jarvis E.E. and Scharff C.(2004). FoxP2 Expression in avian vocal Learners and non- learners. J. Neurosci., 24(13): 3164- 3175. (3) Lu M.M., Li S., Yang H., Morrisey E.E.(2002) FOXP4: a novel member of the Foxp subfamily of winged-helix genes cp-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Mechanisms of Development, 119 Suppl : S197-202. (4) Li S., Weidenfeld J. and Morrisey E.E.(2004) Transcriptional and DNA binding Activity of the Foxp1/2/4 Family is Modulated by Heterotypic and Homotypic Protein interactions. Molecular And Cellular Biology, Vol. 24, No. 2, p.809-822.