In this application, the investigator proposes to screen for new mutations that affect NMJ development in Drosophila. Once new mutations are isolated, the investigator will characterize their phenotypic defects, then characterize the corresponding genes using standard methods available for Drosophila. The investigator will also target expression of an already characterized gene, dlg. Mutations of dlg cause an alteration of a postsynaptic specialization called the subsynaptic reticulum. The research plan of this RCDA application reflects work that will be carried out as part of two grant proposals: a project in a Program Project Grant and an R01 application, the latter is also being reviewed by this study section. In this proposal, the investigator continues work she initiated in her postdoctoral training and first several years as Assistant Professor. That is to use the Drosophila neuromuscular junction as a preparation to examine fundamental features of synaptogenesis via mutations which affect normal development. The preparation appears to be a nice one based on some of the mutations which have already been identified (bpd, wwj, wwf, and paw). Unfortunately, the bulk of the proposed analyses do not deal with any of these mutations, but rather will deal with some new mutations which have not yet been identified. The investigator argues that she would like to gain additional experience in genetic and molecular genetic analysis, presently not possible due to a heavy teaching and administrative load. The main strengths is that synaptogenesis is an excellent problem to approach genetically. The basic biology of the neuromuscular junction preparation is excellent and will get better with analyses proposed elsewhere. The preliminary results are excellent. The main weakness is that the proposal does not build at all on the presented preliminary results on already identified mutations.
| Torroja, L; Packard, M; Gorczyca, M et al. (1999) The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J Neurosci 19:7793-803 |
| Gramates, L S; Budnik, V (1999) Assembly and maturation of the Drosophila larval neuromuscular junction. Int Rev Neurobiol 43:93-117 |
| Koh, Y H; Popova, E; Thomas, U et al. (1999) Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation. Cell 98:353-63 |
| Tejedor, F J; Bokhari, A; Rogero, O et al. (1997) Essential role for dlg in synaptic clustering of Shaker K+ channels in vivo. J Neurosci 17:152-9 |
| Budnik, V; Koh, Y H; Guan, B et al. (1996) Regulation of synapse structure and function by the Drosophila tumor suppressor gene dlg. Neuron 17:627-40 |
| Budnik, V (1996) Synapse maturation and structural plasticity at Drosophila neuromuscular junctions. Curr Opin Neurobiol 6:858-67 |
