Mutation of TweedleD, a member of an unconventional cuticle protein family, alters body shape in Drosophila.

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.

Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund.

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.

Whole-mount analysis reveals normal numbers of dopaminergic neurons following misexpression of alpha-Synuclein in Drosophila.

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.

Structure-function analysis of the Drosophila retinal determination protein Dachshund.

Dachshund (Dac) is a highly conserved nuclear protein that is distantly related to the Ski/Sno family of corepressor proteins. In Drosophila, Dac is necessary and sufficient for eye development and, along with Eyeless (Ey), Sine oculis (So), and Eyes absent (Eya), forms the core of the retinal determination (RD) network. In vivo and in vitro experiments suggest that members of the RD network function together in one or more complexes to regulate the expression of downstream targets.

Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress.

Mutations in the gene parkin in humans (PARK2) are responsible for a large number of familial cases of autosomal-recessive Parkinson disease. We have isolated a Drosophila homolog of human PARK2 and characterized its expression and null phenotype. parkin null flies have 30% lower mass than wild-type controls which is in part accounted for by a reduced cell size and number.

Mechanism of hedgehog signaling during Drosophila eye development.

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 (Ci(rep)).