Choosing sides

The brain carefully conceals its lopsided nature. While it appears outwardly symmetrical, certain functions, like language, are localized preferentially to one side of the brain or the other.

“And because the brain and mind are inextricably linked – the mind is derived from the function of the brain – presumably there are also a number of structural asymmetries as well,” says Josh Gamse, Ph.D., assistant professor of Biological Sciences and Cell & Developmental Biology at Vanderbilt.

Gamse is investigating the origins of brain asymmetry in the zebrafish. Because fish don’t really have much of a cortex – the part of the human brain involved in “higher” cognitive functions – Gamse is looking at an organ, the parapineal organ, which lies in a more primitive part of the brain, the diencephalon.

The parapineal organ is a cluster of neurons in non-mammalian vertebrates that normally migrates from the center of the brain to the left side and directs asymmetric development of other nearby organs, like the habenular nuclei, which are involved in drinking and feeding behavior, some types of learning and mating.

“If you destroy the parapineal early in development, you get symmetric habenular nuclei,” Gamse notes. “So there’s an instructive role – the parapineal tells the left habenula, ‘you’re the left habenula.’”

Gamse and colleagues are now screening mutant zebrafish to find those with disruptions in brain asymmetry and identify the genes that cause the abnormal development.

The asymmetrical brain

Confocal microscopy image shows a greater density of dendrites in the left habenular nuclei of a four-day-old zebrafish larvae compared to the right. The nuclei are involved in drinking and feeding behavior, some types of learning and mating. Studies of asymmetry – structural differences between the two sides of the brain – may provide insights into human disorders such as autism, dyslexia and schizophrenia.

Image by Robert Taylor, graduate student in the lab of Josh Gamse, Ph.D., Vanderbilt University

His group recently identified a mutant zebrafish strain, named from beyond, in which the parapineal organ is smaller (has fewer cells) and remains in the center of the brain. They’ve found that this abnormal symmetry is linked to a mutation in the t-box2b gene, which encodes a transcription factor expressed in the developing parapineal organ.

Identification of genes that underlie the development of asymmetry in this tiny region of the zebrafish brain may help direct the search for the origins of asymmetry in the human brain. Disorders including autism, dyslexia, and schizophrenia have been linked to improper lateralization of the brain, so understanding the biological basis of brain asymmetry may also provide insights into such disorders.