Few other systems are as highly genetically malleable as the worm and fly. The unbiased forward genetic screening approach has led to the identification of a number of molecules involved in synapse development. Advances in cell biology, in vivo imaging, and electrophysiology have led to the characterization of identified synapse development molecules. With these approaches, studies in C. elegans and Drosophila have shed light on many fundamental questions. For example, the use of genetics has revealed entire in vivo signaling mechanisms involved in synapse development, such as the MAPK and TGF-beta pathways. Drosophila and C. elegans cell biology and in vivo imaging have allowed the site-specific dissection of synapse effects. The first large-scale RNAi screen in neuroscience was conducted in C. elegans8. This screen has revealed the immense promise of a functional genomics approach at the synapse. Direct observation of synapse formation in real time would assist our understanding of integrated developmental processes. The valuable Drosophila and C. elegans experimental systems can now be used to integrate the individual processes of synapse development. With great promise, future studies will network the mechanistic interactions and signaling pathways of synapse development.*

'We would like to apologize for not including all relevant studies due to space constraints. We would like to thank Vivian Budnik for the kind contribution of the Drosophila images in Figure 3.1. We would like to thank the following people for helpful comments on the manuscript: C. Weaver, H. Brown, K. Chan, P.C. Spiegel, B. Ackley, C. Suh, and C. Pfeiffenberger. The work in Y.J.'s laboratory is supported by grants from NIH, NSF, and HHMI. Y.J. is an investigator of HHMI.

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