Fog Pathway

MacKay JO, Soanes KH, Srivastava A, Simmonds A, Brook WJ, Bell JB. An in vivo analysis of the vestigial gene in Drosophila melanogaster defines the domains required for Vg function. Genetics. 2003;163(4):1365-1373.

Epithelial-mesenchymal transition (EMT) is a cellular process that is essential for normal processes in many organisms, including embryonic development and wound healing, and is recapitulated in human disease, contributing to organ fibrosis and cancer progression (Thiery et al. 2009; Yang and Weinberg 2008). EMT describes the conversion of a cell with an epithelial phenotype to one with mesenchymal characteristics and can be a partial or complete transformation. Epithelial cells form the borders of tissues and organs, and are characterized by apical-basal polarity, contact with a basement membrane, and strong adherence to other epithelial cells through intercellular junctions including adherens junctions, tight junctions, and desmosomes. Conversely, mesenchymal cells have front-rear polarity and generally lack cell-cell contact, allowing them to be motile. During human embryonic development, EMT is essential for the formation of a variety of tissues, including mesoderm, neural crest, somites, palate, pancreas, liver, reproductive tracts, and heart valves (Thiery et al. 2009; Yang and Weinberg 2008). After development, partial EMT also contributes to wound healing (Thiery et al. 2009). However, EMT can also play a more insidious role by factoring into tumour progression.

Bayer, C.A., Halsell, S.R., Fristrom, J.W., Kiehart, D.P., von Kalm, L. (2003). Genetic interactions between the RhoA and Stubble-stubbloid loci suggest a role for a type II transmembrane serine protease in intracellular signaling during Drosophila imaginal disc morphogenesis. Genetics 165(3): 1417--1432.

Drosophila melanogaster, or the common fruit fly, is a holometabolous insect, meaning it has larval and pupal stages before becoming an adult. At the beginning of development, the D. melanogaster eggs go through syncytial development, which allows for a unique pattern of development. Furthermore, as the egg develops it is surrounded by a thick layer called the chorion, and as two respiratory filaments and a micropyle. Once the egg develops into a larva, it goes through a first, second and third instar stage. In the third instar stage, the imaginal discs and salivary glands develop. The imaginal discs are pockets of epithelium cells that form the adult structures of the organism, including the wings, halters, legs antennae and eyes. The salivary glands are large cells that contain large polytene chromosomes that can be observed when the the glands are stained and squashed.

These receptors are characterized by a seven transmembrane domain, an extracellular region that contains a cysteine-rich domain (CRD), and an intracellular segment that interacts with downstream signaling proteins [42]. The extracellular CRD domain acts as the ligand binding region for most Frizzled receptors [42]. The known ligands of Frizzled receptors are WNTs, R-spondins, Norrins, FRPs (Frizzled related proteins) and CTGF (connective-tissue growth factors) [41]. The Frizzled family receptors are classified as a separate family of GPCRs by IUPHAR, which is largely based on data from sequence comparisons with other GPCR families, the presence of a seven transmembrane segment characteristic to GPCRs, and other indirect evidence that points towards their interactions with G proteins [39,41]. However, direct experimental evidence for their coupling with G protein

(2000) reported that 90% of IBC tumours displayed an over expression of RhoC GTPase, an oncogene that contributes to the invasive nature of IBC. Rho protein activation causes the actin-myosin contractile filaments and focal adhesion complexes to assemble, leading to the formation of lamellipodia. Lamellipodia form at the edge of cells and drive cell migration and motility, furthering metastasis in IBC (Machesky 2008).

DVL 1 protein is a cytoplasmic phosphoprotein produced by DVL 1 gene regulating the cell formations and a transducer particle for the developmental processes such as neuroblast specification and segmentation.1 In Wnt Signalling Pathway, the DVL 1 protein works by binding to C-terminus of frizzled receptors and transduce the wnt signal in both canonical and non-canonical pathway.2 These pathways activation lead to the accumulation of beta catenin protein in the cell which known to have important roles in proliferation and formation of the cells.2

In the year 1924 a paper was published by Hans Spemann and Hilde Mangold, this paper was known as the, “Organizer Paper” (Sander and Faessler, 2001). The Spemann- Mangold organizer, is also known as Spemann Organizer. This experiment showed the initiation of Siamese twins in a transplant experiment with salamander eggs (Robertis 2008). While doing this experiment, Mangold and Spemann called the dorsal blastopore lip in gastrulating frog embryo “the organizer”, the job of the organizer is for initiation which means 1) the organizer imitates gastrulation and also stops signals starting from the ventral side of the blastula from prompting the skin. 2) Separate the host and donor tissues into secondary embryo into an anterior-posterior and dorsal-ventral

Between Dx and Su(dx) mediated endocytic Notch signalling, it has been recently observed that these two pathways can be discriminated (Shimizu et al, unpublished) (Figure 3). Caveolin-1 forms a co-localisation between itself and Notch in relation to the Su(dx) endocytic Notch signalling pathway, but not in the Dx-mediated pathway (Figure 3A). Caveolin-1 is a caveolar coat protein expressed by caveolae, which are invaginations of the plasma membrane associated with endocytosis (Le et al, 2002). Caveoiln-1 is not a protein found within Drosophila, but it can be used to mark lipid raft type membrane domains if it is expressed as a transgene (Allen et al, 2009). Alternatively, it was observed that Clathrin can form a co-localisation between

As a follow-up, Parisiadou et al. showed in 2009 that this neuronal development was regulated by LRRK2 through modulation of ERM (ezrin, radixin and moesin) protein activity and actin polymerisation (Parisiadou et al., 2009). They showed that over-expression of LRRK2 due to the G2019S mutation inhibited neurone outgrowth, increased phosphorylation of ERM proteins and increased the content of F-actin, which is actin that is present in linear polymer microfilaments, in filopodia. ERM proteins are, therefore, thought to be a physiological substrate of the kinase activity of LRRK2. It is this increased presence of ERM proteins that plays a role in the developmental

Cameleons, the first generation of GECIs [161], are chimeric proteins that, in their original iteration, were composed of a blue or cyan FP as a FRET donor and a green or yellow FP as a FRET acceptor. The two FPs are connected by CaM and its binding partner M13 (the CaM-binding domain of myosin light chain kinase) (Figure 6A). A similar design with only the CaM-binding domain was also reported in 1997 [162]. When the CaM domain of a cameleon binds to Ca2+, it changes its conformation and sequentially binds to M13, which results in a more compact conformation that decreases the distance between the FRET donor and acceptor. This decreased distance causes an increase in FRET efficiency that manifests itself as

Eye development is initiated by the master control gene Pax-6, a homeobox gene known as Andridia in humans, small eye in mouse, and eyeless in Drosophila. The Pax-6 gene locus is a transcription factor for the various genes and growth factors involved in eye formation. Eye morphogenesis begins with the evagination, or outgrowth, of the optic grooves or sulci. These two grooves in the neural folds transform into optic vesicles with the closure of the neural tube. The optic vesicles then develop into the optic cup with the inner layer forming the retina

Cell interactions play an important role in cancer progression and my research aims to learn more about how cells interact. I am studying embryo development in C. elegans since this is a time when cells normally interact and move to make sure they are in the correct part of the embryo for normal development. Since known cell adhesion factors do not appear to be solely responsible for cell interactions during development, I am hoping to identify novel genes cell interaction genes by screening for mutants where cells move to the wrong part of the embryo during development. I am observing cells that will develop to form two different tissue types, pharynx and body muscles. To increase the chance of observing mutant interactions, I am using

For example, though the pattern of expression of pair-rule genes may vary across arthropods, they are consistently activated during development and play an important role in determining body segments (Damen, 2007). Compared to genes further upstream in the segmentation pathway, pair-rule genes are highly conserved. The Notch/Delta system is much more divergent among arthropods (Damen, 2007). Though Notch/Delta signaling plays an important role in Drosophila development, it is not greatly involved in segmentation in Drosophila or other insects, but is very important in segmentation in chelicerates (Damen, 2007). Additionally, while gap genes are crucial to determining segmentation in insects, they play a much less significant role in non-insect arthropods like chelicerates and myriapods (Damen, 2007). Genes involved in appendage patterning in arthropods are also highly conserved. The

We leverage the ability of our method for modeling the magnitude of cell morphological changes to identify most significant cell morphological features in response to a compound treatment, and evaluate that its