All neural function depends on the ability of neurons to form precise connections during development. The means by which neuronal growth cones find and recognize their targets is one of the central problems of developmental neurobiology. It is our long-term goal to understand how the growth cones of two photoreceptor cells, R7 and R8, navigate from their points of origin in the Drosophila eye-imaginal disc to their terminal zones in the medulla neuropil, and to identify and characterize the molecules that mediate their pathway choice. By focusing our efforts on understanding the behavior of a small number of neurons in an accessible part of the nervous system, we hope eventually to recover a set of mutations that define the molecular parameters of a single pathway. In our choice of the Drosophila visual system, where the same pathfinding task is repeated 800 times, each slightly displaced in space and time, we are also asking what factors are used to set up a retinotopic map. As a first step toward these goals, we have identified a mutation, misguided (mig), that interrupts these pathways. misguided has several intriguing properties. It appears to be largely restricted to a subset of photoreceptor cells during the development, yet the defect appears in the behavior of the axon, not in the differentiation of the eye. An embryonic neural disruption of an analogous nature (a broadening of normally restricted axonal pathways) is seen along the midline, where the gene is also expressed. We therefore feel this mutation may disrupt a molecule likely to be involved in axonal guidance.Consequently, our specific aims are: (1) to clone the misguided gene by plasmid rescue, taking advantage of a p-insertion that was used to generate the mutation, and to characterize the molecular products of this locus; (2) to generate revertants and new alleles of mig by remobilization of the p-element; (3) to study the distribution and biochemical properties of the mig protein using anti-mig antibodies; (4) to test the function of MU both by observing its effects on the differentiation and viability of the optic anlage, and by deregulating the gene product to explore the meaning of its restricted expression. The information derived from this study will help to refine the parameters used to screen for additional mutations in the behavior of these axons. The similarities of R7 and R8 behavior in the medulla with the behavior of retinal axons in the vertebrate tectum, suggests the information derived from these studies may have wider application.
| Gordon, Y J; Araullo-Cruz, T P; Johnson, Y F et al. (1996) Isolation of human adenovirus type 5 variants resistant to the antiviral cidofovir. Invest Ophthalmol Vis Sci 37:2774-8 |
| Ashley, J A; Katz, F N (1994) Competition and position-dependent targeting in the development of the Drosophila R7 visual projections. Development 120:1537-47 |
| Buckles, G R; Smith, Z D; Katz, F N (1992) mip causes hyperinnervation of a retinotopic map in Drosophila by excessive recruitment of R7 photoreceptor cells. Neuron 8:1015-29 |
