A New Spin on Planar Cell Polarity

The generation of planar cell polarity (PCP) and tissue shape during morphogenesis is tightly linked, but it is not clear how. Aigouy et al. (2010) now show in the developing Drosophila wing that PCP initially has a radial orientation that becomes realigned to the proximal-distal axis of organ shape by mechanical forces and cell rearrangements mediated by Dachsous

Resale value of individual sets of Magic the Gathering

Magic: the Gathering is a strategy-based fantasy card game developed by Richard Garfield in 1993. The appeal of playing the game is found in using cardboard printed cards to cast spells to achieve a victory over one or more opponents. This thesis will provide an analysis of six MTG sets, calculating the average value of one pack of fourteen cards. The relationships between the average resale value for each set will be evaluated using statistical graphical analysis. Conclusions will be drawn regarding the average resale value of a pack of fourteen cards in each of six set

Hibris, a Drosophila Nephrin Homolog, Is Required for Presenilin-Mediated Notch and APP-like Cleavages

SummaryDrosophila Hibris (Hbs), a member of the Nephrin Immunoglobulin Super Family, has been implicated in myogenesis and eye patterning. Here, we uncover a role of Hbs in Notch (N) signaling and γ-secretase processing. Loss of hbs results in classical N-signaling-associated phenotypes in Drosophila, including eye patterning, wing margin, and sensory organ specification defects. In particular, hbs mutant larvae display altered γ-secretase-dependent Notch proteolytic processing. Hbs also interacts molecularly and genetically with Presenilin (Psn) and other components of the γ-secretase complex. This Hbs function appears conserved, as mammalian Nephrin also promotes N signaling in mammalian cells. Our data suggest that Hbs is required for Psn maturation. Consistent with its role in Psn processing, Hbs genetically interacts with the Drosophila β-amyloid protein precursor-like (Appl) protein, the homolog of mammalian APP, the cleavage of which is associated with Alzheimer's disease. Thus, Hbs/Nephrin appear to share a general requirement in Psn/γ-secretase regulation and associated processes

The Atypical Cadherin Flamingo Links Frizzled and Notch Signaling in Planar Polarity Establishment in the Drosophila Eye

AbstractPlanar cell polarity is established in the Drosophila eye through distinct fate specification of photoreceptors R3 and R4 by a two-tiered mechanism employing Fz and Notch signaling: Fz signaling specifies R3 and induces Dl to activate Notch in R4. We show that the atypical cadherin Flamingo (Fmi) plays critical, but distinct, roles in both R3 and R4. Fmi is first enriched at equatorial cell borders of R3/R4, positively interacting with Fz/Dsh. Subsequently, Fmi is upregulated in R4 by Notch and functions to downregulate Dl expression by antagonizing Fz signaling. This in turn amplifies and enforces the initial Fz-signaling bias in the R3/R4 pair. Our results reveal differences in the planar cell polarity genetic circuitry between the eye and the wing

CKIɛ/discs overgrown Promotes Both Wnt-Fz/β-Catenin and Fz/PCP Signaling in Drosophila

SummaryThe related Wnt-Frizzled(Fz)/β-catenin and Fz/planar cell polarity (PCP) pathways are essential for the regulation of numerous developmental processes and are deregulated in many human diseases. Both pathways require members of the Dishevelled (Dsh or Dvl) family of cytoplasmic factors for signal transduction downstream of the Fz receptors. Dsh family members have been studied extensively, but their activation and regulation remains largely unknown. In particular, very little is known about how Dsh differentially signals to the two pathways. Recent work in cell culture has suggested that phosphorylation of Dsh by Casein Kinase I epsilon (CKIɛ) may act as a molecular “switch,” promoting Wnt/β-catenin while inhibiting Fz/PCP signaling [1]. Here, we demonstrate in vivo in Drosophila through a series of loss-of-function and coexpression assays that CKIɛ acts positively for signaling in both pathways, rather than as a switch. Our data suggest that the kinase activity of CKIɛ is required for peak levels of Wnt/β-catenin signaling. In contrast, CKIɛ is a mandatory signaling factor in the Fz/PCP pathway, possibly through a kinase-independent mechanism. Furthermore, we have identified the primary kinase target residue of CKIɛ on Dsh. Thus, our data suggest that CKIɛ modulates Wnt/β-catenin and Fz/PCP signaling pathways via kinase-dependent and -independent mechanisms

Endometrial microbiota — do they mean more than we have expected?

Low biomass microbiome has an increasing importance in today’s fertility studies. There are more and more indicationsfor incorporating upper gynecological tract microbiome content in patients diagnostic and in vitro fertilization process, asdoing so may help to evaluate chances for a positive outcome. An abnormal endometrial microbiota has been associatedwith implantation failure, pregnancy loss, and other gynecological and obstetrical conditions. Furthermore it has beenshown, that using molecular methods in addition to routine diagnostics may help diagnose chronic endometritis or evenindicate cancerogenic changes. Understanding the significance of microbiome in endometrium may completely changetherapeutic approach in treatment of this part of reproductive tract. Next generation sequencing (NGS) has allowed toisolate culturable and unculturable bacteria from female reproductive tract and is a cheaper and quicker alternative forother widely known and used methods

Positioning of centrioles is a conserved readout of Frizzled planar cell polarity signalling

Planar cell polarity (PCP) signalling is a well-conserved developmental pathway regulating cellular orientation during development. An evolutionarily conserved pathway readout is not established and, moreover, it is thought that PCP mediated cellular responses are tissue-specific. A key PCP function in vertebrates is to regulate coordinated centriole/cilia positioning, a function that has not been associated with PCP in Drosophila. Here we report instructive input of Frizzled-PCP (Fz/PCP) signalling into polarized centriole positioning in Drosophila wings. We show that centrioles are polarized in pupal wing cells as a readout of PCP signalling, with both gain and loss-of-function Fz/PCP signalling affecting centriole polarization. Importantly, loss or gain of centrioles does not affect Fz/PCP establishment, implicating centriolar positioning as a conserved PCP-readout, likely downstream of PCP-regulated actin polymerization. Together with vertebrate data, these results suggest a unifying model of centriole/cilia positioning as a common downstream effect of PCP signalling from flies to mammals.Trabajo financiado por: Gobierno de Extremadura. Ayuda para la Atracción y Retención de Talento Investigador, para José María Carvajal GonzálezpeerReviewe

Combinatorial gene regulatory functions underlie ultraconserved elements in Drosophila

Ultraconserved elements (UCEs) are discrete genomic elements conserved across large evolutionary distances. Although UCEs have been linked to multiple facets of mammalian gene regulation their extreme evolutionary conservation remains largely unexplained. Here, we apply a computational approach to investigate this question in Drosophila, exploring the molecular functions of more than 1,500 UCEs shared across the genomes of 12 Drosophila species. Our data indicate that Drosophila UCEs are hubs for gene regulatory functions and suggest that UCE sequence invariance originates from their combinatorial roles in gene control. We also note that the gene regulatory roles of intronic and intergenic UCEs (iUCEs) are distinct from those found in exonic UCEs (eUCEs). In iUCEs, transcription factor (TF) and epigenetic factor binding data strongly support iUCE roles in transcriptional and epigenetic regulation. In contrast, analyses of eUCEs indicate that they are two orders of magnitude more likely than the expected to simultaneously include protein-coding sequence, TF-binding sites, splice sites, and RNA editing sites but have reduced roles in transcriptional or epigenetic regulation. Furthermore, we use a Drosophila cell culture system and transgenic Drosophila embryos to validate the notion of UCE combinatorial regulatory roles using an eUCE within the Hox gene Ultrabithorax and show that its protein-coding region also contains alternative splicing regulatory information. Taken together our experiments indicate that UCEs emerge as a result of combinatorial gene regulatory roles and highlight common features in mammalian and insect UCEs implying that similar processes might underlie ultraconservation in diverse animal taxa

Expression and regulation of caudal in the lower cyclorrhaphan fly Megaselia

The homeobox gene caudal (cad) regulates posterior development in Drosophila. In early embryos, the cad protein (CAD) is expressed in a posterior-to-anterior concentration gradient, which contributes polarity to the developing embryo. The CAD gradient is complementary to and dependent on the anterior pattern organizer Bicoid (BCD), which represses the translation of ubiquitous maternal cad transcripts in the anterior embryo through a direct interaction with the cad 3′ untranslated region (UTR). Here, we show that early embryos of the lower cyclorrhaphan fly Megaselia express the putative cad orthologue Mab-cad throughout the posterior three quarters of the blastoderm but lack maternal transcripts. In transgenic blastoderm embryos of Drosophila, Mab-cad cis-regulatory DNA drives the expression of a reporter gene in a similar pattern, while Mab-cad 3′ UTR fails to mediate translational repression of a ubiquitously transcribed reporter. For another lower cyclorrhaphan fly (Lonchoptera) and two related outgroup taxa of Cyclorrhapha (Empis, Haematopota), we report maternal cad expression in ovarian follicles. Together, our results suggest that BCD is not required for the translational repression of Mab-cad, and that maternal cad expression was lost in the Megaselia lineage