Temporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila

A widely appreciated aspect of developmental robustness is pattern formation in proportion to size. But how such scaling features emerge dynamically remains poorly understood. Here we generate a data set of the expression profiles of six gap genes in Drosophila melanogasterembryos that differ significantly in size. Expression patterns exhibit size-dependent dynamics both spatially and temporally. We uncover a dynamic emergence of under-scaling in the posterior, accompanied by reduced expression levels of gap genes near the middle of large embryos. Simulation results show that a size-dependent Bicoid gradient input can lead to reduced Krüppel expression that can have long-range and dynamic effects on gap gene expression in the posterior. Thus, for emergence of scaled patterns, the entire embryo may be viewed as a single unified dynamic system where maternally derived size-dependent information interpreted locally can be propagated in space and time as governed by the dynamics of a gene regulatory network

Distance measurements via the morphogen gradient of Bicoid in Drosophila embryos

<p>Abstract</p> <p>Background</p> <p>Patterning along the anterior-posterior (A-P) axis in <it>Drosophila </it>embryos is instructed by the morphogen gradient of Bicoid (Bcd). Despite extensive studies of this morphogen, how embryo geometry may affect gradient formation and target responses has not been investigated experimentally.</p> <p>Results</p> <p>In this report, we systematically compare the Bcd gradient profiles and its target expression patterns on the dorsal and ventral sides of the embryo. Our results support a hypothesis that proper distance measurement and the encoded positional information of the Bcd gradient are along the perimeter of the embryo. Our results also reveal that the dorsal and ventral sides of the embryo have a fundamentally similar relationship between Bcd and its target Hunchback (Hb), suggesting that Hb expression properties on the two sides of the embryo can be directly traced to Bcd gradient properties. Our 3-D simulation studies show that a curvature difference between the two sides of an embryo is sufficient to generate Bcd gradient properties that are consistent with experimental observations.</p> <p>Conclusions</p> <p>The findings described in this report provide a first quantitative, experimental evaluation of embryo geometry on Bcd gradient formation and target responses. They demonstrate that the physical features of an embryo, such as its shape, are integral to how pattern is formed.</p

dRecQ4 Is Required for DNA Synthesis and Essential for Cell Proliferation in Drosophila

Background: The family of RecQ DNA helicases plays an important role in the maintenance of genomic integrity. Mutations in three of the five known RecQ family members in humans, BLM, WRN and RecQ4, lead to disorders that are characterized by predisposition to cancer and premature aging. Methodology/Principal Findings: To address the in vivo functions of Drosophila RecQ4 (dRecQ4), we generated mutant alleles of dRecQ4 using the targeted gene knock-out technique. Our data show that dRecQ4 mutants are homozygous lethal with defects in DNA replication, cell cycle progression and cell proliferation. Two sets of experiments suggest that dRecQ4 also plays a role in DNA double strand break repair. First, mutant animals exhibit sensitivity to gamma irradiation. Second, the efficiency of DsRed reconstitution via single strand annealing repair is significantly reduced in the dRecQ4 mutant animals. Rescue experiments further show that both the N-terminal domain and the helicase domain are essential to dRecQ4 function in vivo. The N-terminal domain is sufficient for the DNA repair function of dRecQ4. Conclusions/Significance: Together, our results show that dRecQ4 is an essential gene that plays an important role in no

Uif, a Large Transmembrane Protein with EGF-Like Repeats, Can Antagonize Notch Signaling in Drosophila

<div><h3>Background</h3><p>Notch signaling is a highly conserved pathway in multi-cellular organisms ranging from flies to humans. It controls a variety of developmental processes by stimulating the expression of its target genes in a highly specific manner both spatially and temporally. The diversity, specificity and sensitivity of the Notch signaling output are regulated at distinct levels, particularly at the level of ligand-receptor interactions.</p> <h3>Methodology/Principal Findings</h3><p>Here, we report that the <em>Drosophila</em> gene <em>uninflatable</em> (<em>uif</em>), which encodes a large transmembrane protein with eighteen EGF-like repeats in its extracellular domain, can antagonize the canonical Notch signaling pathway. Overexpression of Uif or ectopic expression of a neomorphic form of Uif, Uif*, causes Notch signaling defects in both the wing and the sensory organ precursors. Further experiments suggest that ectopic expression of Uif* inhibits Notch signaling <em>in cis</em> and acts at a step that is dependent on the extracellular domain of Notch. Our results suggest that Uif can alter the accessibility of the Notch extracellular domain to its ligands during Notch activation.</p> <h3>Conclusions/Significance</h3><p>Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.</p> </div

Trading against disorderly liquidation of a large position under asymmetric information and market impact

We consider trading against a hedge fund or large trader that must liquidate a large position in a risky asset if the market price of the asset crosses a certain threshold. Liquidation occurs in a disorderly manner and negatively impacts the market price of the asset. We consider the perspective of small investors whose trades do not induce market impact and who possess different levels of information about the liquidation trigger mechanism and the market impact. We classify these market participants into three types: fully informed, partially informed and uninformed investors. We consider the portfolio optimization problems and compare the optimal trading and wealth processes for the three classes of investors theoretically and by numerical illustrations

Trading against disorderly liquidation of a large position under asymmetric information and market impact

We consider trading against a hedge fund or large trader that must liquidate a large position in a risky asset if the market price of the asset crosses a certain threshold. Liquidation occurs in a disorderly manner and negatively impacts the market price of the asset. We consider the perspective of small investors whose trades do not induce market impact and who possess different levels of information about the liquidation trigger mechanism and the market impact. We classify these market participants into three types: fully informed, partially informed and uninformed investors. We consider the portfolio optimization problems and compare the optimal trading and wealth processes for the three classes of investors theoretically and by numerical illustrations

Trading against disorderly liquidation of a large position under asymmetric information and market impact

We consider trading against a hedge fund or large trader that must liquidate a large position in a risky asset if the market price of the asset crosses a certain threshold. Liquidation occurs in a disorderly manner and negatively impacts the market price of the asset. We consider the perspective of small investors whose trades do not induce market impact and who possess different levels of information about the liquidation trigger mechanism and the market impact. We classify these market participants into three types: fully informed, partially informed and uninformed investors. We consider the portfolio optimization problems and compare the optimal trading and wealth processes for the three classes of investors theoretically and by numerical illustrations