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

Spatial discontinuity of Optomotor-blind expression in the Drosophila wing imaginal disc disrupts epithelial architecture and promotes cell sorting

<p>Abstract</p> <p>Background</p> <p>Decapentaplegic (Dpp) is one of the best characterized morphogens, required for dorso-ventral patterning of the <it>Drosophila </it>embryo and for anterior-posterior (A/P) patterning of the wing imaginal disc. In the larval wing pouch, the Dpp target gene <it>optomotor-blind </it>(<it>omb</it>) is generally assumed to be expressed in a step function above a certain threshold of Dpp signaling activity.</p> <p>Results</p> <p>We show that the transcription factor Omb forms, in fact, a symmetrical gradient on both sides of the A/P compartment boundary. Disruptions of the Omb gradient lead to a re-organization of the epithelial cytoskeleton and to a retraction of cells toward the basal membrane suggesting that the Omb gradient is required for correct epithelial morphology. Moreover, by analysing the shape of <it>omb </it>gain- and loss-of-function clones, we find that Omb promotes cell sorting along the A/P axis in a concentration-dependent manner.</p> <p>Conclusions</p> <p>Our findings show that Omb distribution in the wing imaginal disc is described by a gradient rather than a step function. Graded Omb expression is necessary for normal cell morphogenesis and cell affinity and sharp spatial discontinuities must be avoided to allow normal wing development.</p

Synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones

2-Substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones were synthesized in three steps from itaconic acid derivatives via cyclization with primary amines followed by Masamune-Claisen condensation, and cyclization of the newly formed β-keto esters with amidines. Preparation and/or isolation of β-keto esters with polar N-substituents failed, but the corresponding final products were obtained in a different way. 6-(1-(3-Hydroxypropyl)-5-oxopyrrolidin-3-yl)-2-phenylpyrimidin-4(3H)-one was obtained by hydrogenolytic o-deprotection of its o-benzyl derivative. Depending on reaction conditions, further mesylation of 6-(1-(3-(benzyloxy)propyl)-5-oxopyrrolidin-3-yl)-2-phenylpyrimidin-4(3H)-one followed by treatment with pyrrolidine gave either the monoaminated- or the diaminated product. The structures of novel compounds were determined by NMR

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

Intergenerational disadvantage: learning about equal opportunity from social assistance receipt

We use variation in the extent of generational persistence across social assistance payments to shed light on the factors leading to intergenerational disadvantage. Our administrative data come from the Australian social security system and provide us with detailed social assistance trajectories – across the entire social safety net – for a birth cohort of young people and their families over an 18-year period. We find that young people are 1.8 times more likely to need social assistance if their parents have a history of receiving social assistance themselves. These young people also receive more intensive support; an additional $12,000 over an 8-year period. The intergenerational correlation is particularly strong in the case of disability payments, payments for those with caring responsibilities, and parenting payments for single parents. Disadvantage stemming from parents’ poor labor market outcomes seems to be easier for young people to overcome. This suggests that parental disadvantage may be more harmful to children’s later life outcomes if it is more strongly driven by circumstances rather than personal choice

Stochastic association of neighboring replicons creates replication factories in budding yeast

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