third larval instar stage, suggesting that larval musculature is intact and that parkin is required only in pupal and adult muscle. parkin flies do not show an age-dependent dopaminergic neuron loss in the brain, even after aging adults for 3 weeks. Nevertheless, degeneration of IFMs demonstrates the importance of parkin in maintaining specific cell groups, perhaps those with a high-energy demand and the concomitant production of high levels of free radicals. parkin mutants will be a valuable model for future analysis of the mechanisms of cell and tissue degeneration.

Body shape determination represents a critical aspect of morphogenesis. In the course of investigating body shape regulation in Drosophila, we have identified a dominant mutation, TweedleD 1 (TwdlD 1 ), that alters overall dimensions at the larval and pupal stages. Characterization of the affected locus led to the discovery of a gene family that has 27 members in Drosophila and is found only among insects. Analysis of gene expression at the RNA and protein levels revealed gene-specific temporal and spatial patterns in ectodermally derived tissues. In addition, light microscopic studies of fluorescently tagged proteins demonstrated that Tweedle proteins are incorporated into larval cuticular structures. This demonstration that a mutation in a Drosophila cuticular protein gene alters overall morphology confirms a role for the fly exoskeleton in determining body shape. Furthermore, parallels between these findings and studies of cuticle collagen genes in Caenorhabditis elegans suggest that the exoskeleton influences body shape in diverse organisms.arthropod ͉ morphogenesis ͉ tandem duplication ͉ Tubby

Drosophila eye development is controlled by a conserved network of retinal determination (RD) genes. The RD genes encode nuclear proteins that form complexes and function in concert with extracellular signal-regulated transcription factors. Identification of the genomic regulatory elements that govern the eye-specific expression of the RD genes will allow us to better understand how spatial and temporal control of gene expression occurs during early eye development. We compared conserved non-coding sequences (CNCSs)between five Drosophilids along the ∼40 kb genomic locus of the RD gene dachshund (dac). Our analysis uncovers two separate eye enhancers in intron eight and the 3′ non-coding regions of the dac locus defined by clusters of highly conserved sequences. Loss-and gain-of-function analyses suggest that the 3′ eye enhancer is synergistically activated by a combination of eya, so and dpp signaling, and only indirectly activated by ey, whereas the 5′ eye enhancer is primarily regulated by ey, acting in concert with eya and so. Disrupting conserved So-binding sites in the 3′ eye enhancer prevents reporter expression in vivo. Our results suggest that the two eye enhancers act redundantly and in concert with each other to integrate distinct upstream inputs and direct the eye-specific expression of dac.

Although Hedgehog (Hh) signaling is essential for morphogenesis of the Drosophila eye, its exact link to the network of tissue-specific genes that regulate retinal determination has remained elusive. In this report, we demonstrate that the retinal determination gene eyes absent (eya) is the crucial link between the Hedgehog signaling pathway and photoreceptor differentiation. Specifically, we show that the mechanism by which Hh signaling controls initiation of photoreceptor differentiation is to alleviate repression of eya and decapentaplegic (dpp) expression by the zinc-finger transcription factor Cubitus interruptus (Cirep). Furthermore, our results suggest that stabilized, full length Ci (Ciact) plays little or no role in Drosophila eye development. Moreover, while the effects of Hh are primarily concentration dependent in other tissues, hh signaling in the eye acts as a binary switch to initiate retinal morphogenesis by inducing expression of the tissue-specific factor Eya.

Previously published reports have suggested that misexpression of alpha-Synuclein in the Drosophila central nervous system causes neurodegeneration and progressive age-dependent locomotor dysfunction similar to pathologic and clinical manifestations of Parkinson's disease. The number of dopaminergic (DA) neurons in these studies was assessed using immunohistochemistry with an anti-tyrosine hydroxylase antibody on sequential paraffin sections of fly brains. In contrast, we do not observe any DA cell loss in alpha-Synuclein expressing fly brains when using whole-mount immunohistochemistry as an assay. Our results suggest that the DA cell loss observed with misexpression of alpha-Synuclein is not fully penetrant under a variety of experimental conditions and that this may complicate interpretation of such experiments.