miR-9 regulates basal ganglia-dependent developmental vocal learning and adult vocal performance in songbirds

摘要

When a cell needs to make a protein, it makes a temporary copy of the corresponding gene so that the genetic code can be carried to its protein-making machinery. When the temporary copy of the code is no longer needed, the cell destroys it. This system is fine-tuned by other small stretches of genetic code called microRNAs, which speed up the destruction and so help to switch genes off faster. Two genes called FOXP1 and FOXP2 are known to have roles in speech and language development in humans. When these genes do not work properly, people have severe difficulties when speaking and understanding speech. But scientists know little about how the brain controls them. The brains of animals with backbones – like birds and mammals – make a microRNA called miR-9. Scientists thought miR-9 may control how active the FOXP1 and FOXP2 genes are in the brain. Like humans, zebra finches communicate vocally. Young male birds learn to sing by imitating the song of an adult tutor, usually their father. The process is controlled by a brain region called “Area X”. Now, Shi et al. report on the role of miR-9 in vocal learning and singing in zebra finches. First, the gene for miR-9 was inserted into a virus-based genetic tool. Shi et al. then injected this virus into Area X of juvenile zebra finches, which delivered the gene to the brain cells and forced them to make excess miR-9. A control group received empty virus with no miR-9 gene for comparison. The juvenile finches then grew up with an adult bird that taught them to sing. Shi et al. found that the birds that overproduced miR-9 did not learn as well as their normal counterparts. Their songs were shorter, they stuttered, and they missed out syllables, which meant that they simply sounded different to their tutors. These young birds also failed to change their tune in different situations, for example, when they met a female zebra finch. Examination of the birds’ brains four weeks after the viral injection showed that the bird versions of the FOXP1 and FOXP2 genes were less active. There were also changes in other genes involved in brain circuit development. Humans have a brain area like Area X, called the basal ganglia. The link between miR-9 and vocal learning provides a starting point to understand more about language in general. This could lead to improved understanding of conditions like stuttering, Tourette’s syndrome, dyslexia and autism spectrum disorders.