§ Lehrstuhl für Entwicklungsbiologie, Universität Regensburg, Universitätsstr. 31, D-93040 Regensburg, # Dept. of Biological Chemistry and HHMI, Univ. of California, Los Angeles,
Mutants for the 3rd. chromosomal genes nonstop (not) and quo vadis (quo) show a strong hyperinnervation of the medulla anlage by photoreceptor axons [Martin et al. (‘95) Neuron 14]. This phenotype reflects a change in target site specificity of photoreceptor neurons R1-R6. Mutant R1-R6 growth cones pass their wild type terminal region, the lamina, and terminate in the target area of photoreceptor neurons R7 and R8, the medulla. This suggests that the growth cones are unable to interpret signals from their proper target or alternatively, the lamina might lack the substrate to induce the selective termination of R1-R6 growth cones. Mosaic studies suggest a requirement of quo in the eye. In adult escapers of the pupal lethal mutation, many photoreceptor axons are misrouted around the medulla neuropil. Although they finally terminate in the proper layer of the medulla neuropil they do not project in a retinotropic fashion. There are no changes in the cell fate of the R-cells as assesed in the adult eyes of escapers and in mosaic patches. Analysis of several enhancer trap lines and the S-phase pattern of dividing optic lobe neuroblasts in quo mutant larvae suggest an additional role of the quo gene in the development of the inner optic anlage. A subset of lamina glia cells seems to be altered in their differentiation program, however mosaic studies indicate that the targeting defects map to the eye. In contrast to quo, mosaic analysis of not suggests that it is required in the optic lobes and not in the eye. Analysis of several markers of the outer optic anlage did not show any major disturbances in the lamina and medulla in not mutants. Expression of the LPC-specific marker PZA8 [Perez and Steller, pers. communication] is indistinguishable from wildtype and, although many R1-R6 axons grow through the lamina, the LPCs undergo their innervation-dependent final round of S-phases. As judged by the expression of the Dachshund protein [Mardon (’94) Dev. 120 (12)] lamina neurons go on to differentiate. Two pupal lethal alleles of not (the EMS induced allele not1 and a P-element line from the Dros. Genome Project, not2) have been characterized; not2 is likely a null allele, since the P-element is inserted in the N-terminal coding region. Plasmid rescue was used for the cloning of the not gene and data base searches revealed a homology of Not to several ubiquitin hydrolases including the human oncogene tre-2, the yeast protease UBP-J and the Drosophila Faf protein. The not transcript is expressed in the CNS in the third larval instar; particularly in the LPCs that migrate through the furrow of the lamina anlage, where they make contact to the R1-R6 growth cones. Studies are in progress to asses the role of not in this interaction.