Wingless signaling and the control of cell shape in Drosophila wing imaginal discs

AbstractThe control of cell morphology is important for shaping animals during development. Here we address the role of the Wnt/Wingless signal transduction pathway and two of its target genes, vestigial and shotgun (encoding E-cadherin), in controlling the columnar shape of Drosophila wing disc cells. We show that clones of cells mutant for arrow (encoding an essential component of the Wingless signal transduction pathway), vestigial or shotgun undergo profound cell shape changes and are extruded towards the basal side of the epithelium. Compartment-wide expression of a dominant-negative form of the Wingless transducer T-cell factor (TCF/Pangolin), or double-stranded RNA targeting vestigial or shotgun, leads to abnormally short cells throughout this region, indicating that these genes act cell autonomously to maintain normal columnar cell shape. Conversely, overexpression of Wingless, a constitutively-active form of the Wingless transducer β-catenin/Armadillo, or Vestigial, results in precocious cell elongation. Co-expression of Vestigial partially suppresses the abnormal cell shape induced by dominant-negative TCF. We conclude that Wingless signal transduction plays a cell-autonomous role in promoting and maintaining the columnar shape of wing disc cells. Furthermore, our data suggest that Wingless controls cell shape, in part, through maintaining vestigial expression

Flexibility within the middle ears of vertebrates

Introduction and aims: Tympanic middle ears have evolved multiple times independently among vertebrates, and share common features. We review flexibility within tympanic middle ears and consider its physiological and clinical implications. Comparative anatomy: The chain of conducting elements is flexible: even the ‘single ossicle’ ears of most non-mammalian tetrapods are functionally ‘double ossicle’ ears due to mobile articulations between the stapes and extrastapes; there may also be bending within individual elements. Simple models: Simple models suggest that flexibility will generally reduce the transmission of sound energy through the middle ear, although in certain theoretical situations flexibility within or between conducting elements might improve transmission. The most obvious role of middle-ear flexibility is to protect the inner ear from high-amplitude displacements. Clinical implications: Inter-ossicular joint dysfunction is associated with a number of pathologies in humans. We examine attempts to improve prosthesis design by incorporating flexible components

Proceedings of the 1998 Winter Simulation Conference

Traditional methods of dealing with variability in simulation input data are mainly stochastic. This is most often the best method to use if the factors affecting the variation or the nature of the relationships between the factors and the outputs can not be easily identified

Stochastic association of neighboring replicons creates replication factories in budding yeast

Peer reviewedPublisher PD

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

Ipl1/aurora kinase suppresses S-CDK-driven spindle formation during prophase I to ensure chromosome integrity during meiosis

Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK) during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics

Cytoneme-Mediated Delivery of Hedgehog Regulates the Expression of Bone Morphogenetic Proteins to Maintain Germline Stem Cells in Drosophila

Genetic manipulation of the germline stem cell niche in Drosophila ovaries reveals that support cells ensure the maintenance of stem cells by modulating the spread of Hedgehog within the niche

Characterization of the Drosophila Ortholog of the Human Usher Syndrome Type 1G Protein Sans

BACKGROUND: The Usher syndrome (USH) is the most frequent deaf-blindness hereditary disease in humans. Deafness is attributed to the disorganization of stereocilia in the inner ear. USH1, the most severe subtype, is associated with mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15, and sans. Myosin VIIa, harmonin, cadherin 23, and protocadherin 15 physically interact in vitro and localize to stereocilia tips in vivo, indicating that they form functional complexes. Sans, in contrast, localizes to vesicle-like structures beneath the apical membrane of stereocilia-displaying hair cells. How mutations in sans result in deafness and blindness is not well understood. Orthologs of myosin VIIa and protocadherin 15 have been identified in Drosophila melanogaster and their genetic analysis has identified essential roles in auditory perception and microvilli morphogenesis, respectively. PRINCIPAL FINDINGS: Here, we have identified and characterized the Drosophila ortholog of human sans. Drosophila Sans is expressed in tubular organs of the embryo, in lens-secreting cone cells of the adult eye, and in microvilli-displaying follicle cells during oogenesis. Sans mutants are viable, fertile, and mutant follicle cells appear to form microvilli, indicating that Sans is dispensable for fly development and microvilli morphogenesis in the follicle epithelium. In follicle cells, Sans protein localizes, similar to its vertebrate ortholog, to intracellular punctate structures, which we have identified as early endosomes associated with the syntaxin Avalanche. CONCLUSIONS: Our work is consistent with an evolutionary conserved function of Sans in vesicle trafficking. Furthermore it provides a significant basis for further understanding of the role of this Usher syndrome ortholog in development and disease