Speech and language disorders affect millions of people in the United States. A new LSU Health Sciences Center bird study has identified two tiny molecules as potential regulators of a gene whose mutations cause these impairments. It represents a finding that may have implications for humans.
Led by Dr. Xiao Ching Li at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence and published recently in The Journal of Neuroscience, the three-year study is another step in research that began in 2001, when scientists in England first identified the gene FOXP2 as being linked to speech and language. The scientists studied a family (known only as the "KE" family) who suffered from severe speech and language disorders. Almost half of its members, across three generations, had these impairments. Studies revealed a chromosomal defect affecting the FOXP2 gene, known as the "language" gene (though it is not the only gene associated with language). Further genetic studies in other people with the same types of disorders confirmed that mutations in the gene are linked to speech and language disorders.
"FOXP2 controls the expression of other genes — several hundred of them — and is very important in the neurocircuits for language," Li says. "We also know it has to be precisely regulated, with too much or too little being a problem. What we realized is that we didn't know what controls FOXP2."
Li hypothesized that microRNAs (miRNAs) might be involved in controlling the language gene. MiRNAs are molecules that regulate the expression of genes.
Li and her team tested their hypothesis on zebra finches, because the vocal learning process in birds is similar to speech and language development in humans, and the underlying sequence and expression of the FOXP2 gene is very similar among higher vertebrates. The team was the first to identify two miRNAs regulating the levels of FOXP2. MiRNAs prevent the production of a particular protein by binding to and destroying the messenger RNA that would have produced the protein. The researchers found that certain microRNAs target specific sequences in the zebra finches' FOXP2 (three prime untranslated regions) and decrease the FOXP2 protein and mRNA expression. Li and her team's hypothesis turned out to be correct.
Li and her team also found that in a zebra finch's brain, these miRNAs are expressed in a structure (the basal ganglia nucleus) that is required for vocal learning and that their function is regulated during that learning process. The researchers also found that the expression of the miRNAs is regulated by the social context of song behavior, specifically in males singing "undirected" songs. ("Undirected" songs are those sung in solitude, while "directed" songs are those used in courtship.)
So what do these findings represent? This study shows a mechanism that regulates FOXP2 expression and suggests that social vocal behavior can influence how language is learned.
In layperson's terms, the finding represents another piece of the puzzle, Li says. "Our next specific step is to find out if by changing the miRNA, will we change FOXP2?" Li says. "We need to see what its impact is on vocal learning behavior."
As for the study's long-term implications and its affect on humans, Li says, "The insights we obtained from studying birds are highly relevant to speech and language in humans and related neural developmental disorders, such as autism. Understanding how miRNAs regulate FOXP2 may open possibilities to influence speech and language development through genetic variations in miRNA genes, as well as behavioral and environmental factors."
Dr. Li's research was funded by the National Institutes of Health and the Brain and Behavior Research Foundation. Her research team included Zhimin Shi, Ph.D., and Lijuan Fu, Ph.D., from the LSU Health Sciences Center New Orleans Neuroscience Center; Zhide Fang, Ph.D., from the LSU Health Sciences Center New Orleans School of Public Health; and Guanzheng Luo, Ph.D., and XiuJie Wang, Ph.D., from the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences.