By DANIEL STRAIN - AAAS & PLOS
Added: Sun, 10 Jul 2011 14:45:40 UTC

AAAS

Stretching out. When budding neurons get a healthy dose of FOXP2, they tend to grow longer limbs (right) compared with brain cells cut off from the protein (left).
Credit: Adapted from S. C. Vernes et al., PLoS Genetics, 7 (July 2011)

A protein in the brain that has been linked to the development of human language may push developing neurons to reach out and touch someone—or, at least, other brain cells, according to a new study. Such early links could organize the cell-to-cell connections critical for learning complex tasks later in life, including reciting Dr. Seuss, researchers say.

Researchers first identified the FOXP2 gene and its protein in 2001. The study involved a family that had difficulty pronouncing and understanding words, and since then scientists have suspected that the gene may have played a role in the evolution of human language. It even appears to be important to "speech" in other animals: zebra finches with low levels of the FOXP2 protein, for example, can't learn the songs that other birds sing.

Most studies of FOXP2 have focused on its effects post-birth, says Simon Fisher, a neurogeneticist at the Max Planck Institute for Psycholinguistics in Nijmegen, Netherlands. So scientists have been unclear about its role in very early brain building.

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PLoS

Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain

Abscract
Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections.

TAGGED: BIOLOGY