To form the correct circuitry in the developing nervous system, billions of nerve cells must send their axons (individual nerve fibers) over long distances to find their specific target cells. How these axons find their targest is one of the fundamental questions of developmental neuroscience. When many axons take similar pathways and form a nerve bundle or axon tract, individual axons are often highly organized within the larger tract. How such sorting within axon tracts is achieved is a basic question of axon guidance that has been studied very little.
In the visual system, retinal axons exit the eye and form the optic nerve, where they are organized in a very precise array according to their point of origin. Shortly after passing through the optic chiasm, these retinal axons reorganize in a characteristic way, so that they are sorted out according to a different order as they grow through the optic tract on their way to visual centers in the brain. This sorting of retinal axons in the optic tract allow the proper formation of normal visual connections, and is therefore critical for normal vision.
This project will study the mechanisms of axon sorting in the visual system of the zebrafish, Danio rerio. The zebrafish visual system has many fundamental similarities (both genetic and anatomical) to humans and other vertebrates, and so the principles discovered here are likely to have wide applicability. In a particular zebrafish mutant strain, called boxer, a subset of the retinal axons fail to reorganize normally within the optic tract. Thus, normal function of the boxer gene is critical for normal development of the visual system. The proposed experiments will analyze whether boxer function is required in the eye or in the brain, and will clone boxer to determine which mutated gene is responsible for the visual system defect. These experiments will shed light on a critical aspect of how the brain is properly wired during development.
