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Functional characterization of FoxP2 in vitro and in vivo

Sebastian Haesler, Doctoral Student
Christelle Rochefort, Postdoctoral Student

FOXP2 is the first gene implicated in the human specific traits speech and language because mutations of FOXP2 (a member of the winged-helix/forkhead box transcription factor gene family) were identified in individuals with severe difficulty articulating speech [1]. Morphological and functional analysis of patients' brain implicate the basal ganglia in the etiology of the impairment [2]. Since song learning in birds critically depends on the basal ganglia, we are interested in the role of FoxP2 in the development and function of song-relevant neural circuitry in zebra finches.

In a previous study we found that FoxP2 is expressed in the songbird forebrain, predominantly in neurons of the basal ganglia, the brain region most affected in patients with FOXP2 mutations. Strikingly, within the male zebra finch striatum, FoxP2 was upregulated specifically in Area X, a nucleus essential for vocal learning, at the age when vocal learning occurs. Thus, place and time of FoxP2 expression in the avian Area X are compatible with a role in learned vocal communication [3].

We are currently functionally characterizing FoxP2 on the molecular level in vitro and in the living animal using a lentiviral expression.

  (1) Lai, C.S., et al., A forkhead-domain gene is mutated in a severe speech and language disorder. Nature, 2001. 413(6855): p. 519-23. (2) Vargha-Khadem, F., et al., Neural basis of an inherited speech and language disorder. Proc Natl Acad Sci U S A, 1998. 95(21): p. 12695-700. (3) Haesler, S., et al., FoxP2 expression in avian vocal learners and non-learners. J Neurosci, 2004. 24(13): p. 3164-75. (4) Dykxhoorn, D.M., C.D. Novina, and P.A. Sharp, Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol, 2003. 4(6): p. 457-67.