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The Journal of Neuroscience, March 31, 2004, 24(13):3152-3163; doi:10.1523/JNEUROSCI.5589-03.2004

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Behavioral/Systems/Cognitive
Parallel FoxP1 and FoxP2 Expression in Songbird and Human Brain Predicts Functional Interaction

Ikuko Teramitsu,¹ Lili C. Kudo,² Sarah E. London,² Daniel H. Geschwind,^2,4 and Stephanie A. White^1,2,3

Interdepartmental Programs in ¹Molecular, Cellular, and Integrative Physiology, and ²Neuroscience, ³Department of Physiological Science and the Brain Research Institute, and ⁴Department of Neurology and Neurogenetics Program in the David Geffen School of Medicine, University of California, Los Angeles, California 90095

Humans and songbirds are two of the rare animal groups that modify their innate vocalizations. The identification of FOXP2 as the monogenetic locus of a human speech disorder exhibited by members of the family referred to as KE enables the first examination of whether molecular mechanisms for vocal learning are shared between humans and songbirds. Here, in situ hybridization analyses for FoxP1 and FoxP2 in a songbird reveal a corticostriatal expression pattern congruent with the abnormalities in brain structures of affected KE family members. The overlap in FoxP1 and FoxP2 expression observed in the songbird suggests that combinatorial regulation by these molecules during neural development and within vocal control structures may occur. In support of this idea, we find that FOXP1 and FOXP2 expression patterns in human fetal brain are strikingly similar to those in the songbird, including localization to subcortical structures that function in sensorimotor integration and the control of skilled, coordinated movement. The specific colocalization of FoxP1 and FoxP2 found in several structures in the bird and human brain predicts that mutations in FOXP1 could also be related to speech disorders.

Key words: forkhead; language; song; speech; vocal learning; zebra finch

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Received Sep 22, 2003; revised January 23, 2004; accepted January 26, 2004.

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