A major challenge in developmental neurobiology is to understand the formation of topographic maps, in which the positional information of sensory neurons is maintained by their axons as they project to the central nervous system. In the visual system, the formation of topographic maps is essential for an organism to maintain an accurate spatial representation of the external world. In the zebrafish retinotectal system, retinal ganglion cells (RGCs) project to cells in their primary target organ, the optic tectum, along two topographic axes, anterior-posterior (A-P) and dorsal-ventral (D-V). The molecular mechanisms underlying the formation of retinotectal topography along the A-P axis have been largely elucidated. However, it is not known how D-V topography is established in the retinotectal system. Recently, a large-scale screen for mutations in the zebrafish retinotectal system yielded the mutant nevermind (nev). In this mutant, axons from dorsal RGCs missort with axons from ventral RGCs in the optic tract and project incorrectly to both the dorsal and ventral optic rectum rather than just the ventral optic tectum. The following specific aims are designed to test how nev regulates D-V topographic mapping in the zebrafish retinotectal system.
In Specific Aim 1, I will determine how and where the nev mutation affects the formation of D-V topography in the retinotectal projection.
In Specific Aim 2, I will determine the map position of nev and clone the affected gene. Comparison with the known mechanisms of anterior-posterior topography will contribute to an understanding of the general principles that govern the formation of topographic maps.
| Pittman, Andrew J; Gaynes, John A; Chien, Chi-Bin (2010) nev (cyfip2) is required for retinal lamination and axon guidance in the zebrafish retinotectal system. Dev Biol 344:784-94 |
