Oliver Hobert, Columbia University; Miguel Concha, University of Chile; and Christopher Walsh, Harvard Medical School, are making early inroads into the origins of asymmetry in the brain.

In some important circumstances, however, asymmetry rules. Hobert, a fan of the intricate, repeating, and symmetrical geometries of Islamic art and architecture, focuses his research on the asymmetrical nature of the brain. Outwardly, it appears to be made up of a matched pair of gray, wrinkled hemispheres. But on closer inspection, certain brain regions have broken symmetry in terms of shape, structure, size, or function. The two sides of the human brain differ most radically in the way they process information. In effect, the two hemispheres "think" in contrasting ways. The left side controls speech and language processing, math, and logical thought, while the right hemisphere deals in spatial and face recognition, emotional control, and artistic abilities.

Fossil evidence suggests that left-brain, right-brain differences began showing up in the expanding brains of prehuman hominids around 2 million years ago. Present-day nonhuman primates also show brain asymmetries, though they are less pronounced than in humans. Asymmetric brain structures are probably widespread and have been discovered in creatures as varied as chickens, toads, fish, bees, and worms, including the roundworm Caenorhabditis elegans.

The first discoveries of functions localized in different hemispheres of the human brain came about 150 years ago, when speech and language were traced to left-hemisphere locations that weren't duplicated in the right half. Since then, many other specialized functions have been traced to one hemisphere or the other, and the field has lately been given fresh impetus with tools such as confocal microscopy, novel animal models, techniques for tagging cells with antibodies and fluorescent proteins, and large-scale gene-expression analyses.

Breaking symmetry involves some very complex biology in the course of embryonic development. Starting out as a ball of identical cells, the embryo divides along axes—head and tail, front and back, left and right sides. Initially, the cells on the two sides of the brain are identical, but they differentiate in response to genetic signals. The question is not only how they become different from each other, but what determines whether a cell is "left" or "right?"

Fortunately for neuroscientists, brain asymmetries have been identified in two of the simple, well-understood model organisms routinely used in developmental studies—the nematode C. elegans and the striped, minnow-like zebrafish. (The geneticist's favorite model, the fruit fly, has not been of much use here as not many asymmetries have been found in its brain.)

"Our goal is to use zebrafish to look at asymmetries to see how they are generated, from genes through circuitry to behavior," says Stephen Wilson, professor of developmental genetics at University College, London. The zebrafish has a number of convenient qualities, including a small but "conspicuous" brain asymmetry and the fact that its embryos are transparent, says Miguel L. Concha, an HHMI international research scholar at the University of Chile in Santiago, who began probing the creature's brain asymmetries as a postdoc in Wilson's lab.

Concha has created transgenic zebrafish that express green fluorescent protein in developing brain cells; using a microscope and video camera, he can follow the glowing cells as they divide and move about to assemble the brain. He and Wilson have focused on two asymmetrical brain components whose development can be tracked: a pair of groups of neurons called the habenulae (a switching station for a variety of nerve cells) and a related light-sensitive organ called the parapineal nucleus, which generates some of the left-sided wiring that makes that side of the brain different from the right.

Photos: Hobert: Clark Jones / AP, © HHMI, Concha: Eloisa Llorea, Walsh: Joshua Dalsimer

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