Microbiology Commons^™

Cell Type-Specific Responses To Wingless, Hedgehog And Decapentaplegic Are Essential For Patterning Early Eye-Antenna Disc In Drosophila, Jong-Hoon Won, Orkhon Tsogtbartarr, Wonseok Son, Amit Singh, Kwang-Wook Choi, Kyung-Ok Cho

Biology Faculty Publications

The Drosophila eye-antenna imaginal disc (ead) is a flattened sac of two-layered epithelia, from which most head structures are derived. Secreted morphogens like Wingless (Wg), Hedgehog (Hh), and Decapentaplegic (Dpp) are important for early patterning of ead, but the underlying mechanisms are still largely unknown. To understand how these morphogens function in the ead of early larval stages, we used wg-LacZ and dpp-Gal4 markers for the examination of wild-type and mutant eads. We found that the ead immediately after hatching was crescent-shaped with the Bolwig’s nerve at the ventral edge, suggesting that it consists of dorsal domain. In a subsequent …

Intercellular Cooperation And Competition In Brain Cancers: Lessons From Drosophila And Human Studies, Indrayani Waghmare, Austin Roebke, Mutsuko Minata, Madhuri Kango-Singh, Ichiro Nakano

Biology Faculty Publications

Glioblastoma (GBM) is a primary brain cancer with an extremely poor prognosis. GBM tumors contain heterogeneous cellular components, including a small subpopulation of tumor cells termed glioma stem cells (GSCs). GSCs are characterized as chemotherapy- and radiotherapy-resistant cells with prominent tumorigenic ability. Studies in Drosophila cancer models demonstrated that interclonal cooperation and signaling from apoptotic clones provokes aggressive growth of neighboring tumorigenic clones, via compensatory proliferation or apoptosis induced proliferation. Mechanistically, these aggressive tumors depend on activation of Jun-N-terminal kinase (upstream of c-JUN), and Drosophila Wnt (Wg) in the apoptotic clones. Consistent with these nonmammalian studies, data from several mammalian …

Chip-Seq And Rna-Seq Reveal An Amrz-Mediated Mechanism For Cyclic Di-Gmp Synthesis And Biofilm Development By Pseudomonas Aeruginosa, Christopher J. Jones, David Newsom, Benjamin Kelly, Yasuhiko Irie, Laura K. Jennings, Binjie Xu, Dominique H. Limoli, Joe J. Harrison, Matthew R. Parsek, Peter White, Daniel J. Wozniak

Biology Faculty Publications

The transcription factor AmrZ regulates genes important for P. aeruginosa virulence, including type IV pili, extracellular polysaccharides, and the flagellum; however, the global effect of AmrZ on gene expression remains unknown, and therefore, AmrZ may directly regulate many additional genes that are crucial for infection. Compared to the wild type strain, a ΔamrZ mutant exhibits a rugose colony phenotype, which is commonly observed in variants that accumulate the intracellular second messenger cyclic diguanylate (c-di-GMP). Cyclic di-GMP is produced by diguanylate cyclases (DGC) and degraded by phosphodiesterases (PDE). We hypothesized that AmrZ limits the intracellular accumulation of c-di-GMP through transcriptional repression …

Novel Neuroprotective Function Of Apical-Basal Polarity Genecrumbs In Amyloid Beta 42 (Aβ42) Mediated Neurodegeneration, Andrew Steffensmeier, Meghana Tare, Oorvashi Roy Puli, Rohan Modi, Jaison Nainaparampil, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer's disease (AD, OMIM: 104300), a progressive neurodegenerative disorder with no cure to date, is caused by the generation of amyloid-beta-42 (Aβ42) aggregates that trigger neuronal cell death by unknown mechanism(s). We have developed a transgenic Drosophilaeye model where misexpression of human Aβ42 results in AD-like neuropathology in the neural retina. We have identified an apical-basal polarity gene crumbs (crb) as a genetic modifier of Aβ42-mediated-neuropathology. Misexpression of Aβ42 caused upregulation of Crb expression, whereas downregulation of Crb either by RNAi or null allele approach rescued the Aβ42-mediated-neurodegeneration. Co-expression of full length Crb with Aβ42 increased severity of Aβ42-mediated-neurodegeneration, …

Recurrent Modification Of A Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity, William A. Rogers, Joseph R. Salomone, David J. Tacy, Eric M. Camino, Kristen A. Davis, Mark Rebeiz, Thomas M. Williams

Biology Faculty Publications

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. InDrosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development …

Scribble Acts In The Drosophila Fat-Hippo Pathway To Regulate Warts Activity, Shilpi Verghese, Indrayani Waghmare, Hailey Kwon, Katelin Hanes, Madhuri Kango-Singh

Biology Faculty Publications

Epithelial cells are the major cell-type for all organs in multicellular organisms. In order to achieve correct organ size, epithelial tissues need mechanisms that limit their proliferation, and protect tissues from damage caused by defective epithelial cells. Recently, the Hippo signaling pathway has emerged as a major mechanism that orchestrates epithelial development. Hippo signaling is required for cells to stop proliferation as in the absence of Hippo signaling tissues continue to proliferate and produce overgrown organs or tumors. Studies in Drosophila have led the way in providing a framework for how Hippo alters the pattern of gene transcription in target …

Fluorescence-Based Reporter For Gauging Cyclic Di-Gmp Levels In Pseudomonas Aeruginosa, Morten T. Rybtke, Bradley R. Borlee, Keiji Murakami, Yasuhiko Irie, Morten Hentzer, Thomas E. Nielsen, Michael Givskov, Matthew R. Parsek, Tim Tolker-Nielsen

Biology Faculty Publications

The increased tolerance toward the host immune system and antibiotics displayed by biofilm-forming Pseudomonas aeruginosa and other bacteria in chronic infections such as cystic fibrosis bronchopneumonia is of major concern. Targeting of biofilm formation is believed to be a key aspect in the development of novel antipathogenic drugs that can augment the effect of classic antibiotics by decreasing antimicrobial tolerance. The second messenger cyclic di-GMP is a positive regulator of biofilm formation, and cyclic di-GMP signaling is now regarded as a potential target for the development of antipathogenic compounds. Here we describe the development of fluorescent monitors that can gauge …

Neurodegeneration - A Means To An End, Amit Singh

Biology Faculty Publications

Cell death, a global phenomenon found throughout the animal kingdom, is a mechanism to maintain tissue homeostasis and for adaptation to changes in the environment [1,2]. Millions of cells die in our body daily- they succumb to stress and commit suicide by a mechanism referred to as cell death or apoptosis [2-4]. Under normal conditions cells are continuously replaced by new cells from the stemor progenitor- cells. For example, an optimum balance in shedding of dead cells from the skin and their replenishment by new ones maintain our health and hygiene. In this context, apoptosis is a mechanism to eliminate …

Tumor Suppression By Cell Competition Through Regulation Of The Hippo Pathway, Chiao-Lin Chen, Molly C. Schroeder, Madhuri Kango-Singh, Chunyao Tao, Georg Halder

Biology Faculty Publications

Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer. However, the underlying mechanisms of this surveillance are poorly understood. Here we investigated how clones of cells mutant for the neoplastic tumor suppressor gene scribble (scrib) are eliminated from Drosophila imaginal discs. When all cells in imaginal discs are mutant for scrib, they hyperactivate the Hippo pathway effector Yorkie (Yki), which drives growth of the discs into large neoplastic masses. Strikingly, when discs also contain normal cells, the scrib− cells do not overproliferate and eventually undergo apoptosis through JNK-dependent mechanisms. However, induction of apoptosis does …

Protein Trap Lines Of Drosophila To Demonstrate Spatio-Temporal Localization Of Proteins In An Undergraduate Lab, Oorvashi Roy Puli, Amit Singh

Biology Faculty Publications

The objective of this teaching note is to generate a laboratory exercise, which allows students to get a hands-on experience of a cell biology technique. The short duration of the laboratory classes is the biggest challenge with the development of a cell biology lab for an undergraduate curriculum. Therefore, it is necessary to design a laboratory exercise that enables the students to carry out cell biological assays in the desired time. This laboratory exercise focuses on tracking protein expression levels along a spatial (space) and temporal (time) axis in developing Drosophila melanogaster organ primordium. Here we use the protein trap …

Quantitative Comparison Of Cis-Regulatory Element (Cre) Activities In Transgenic Drosophila Melanogaster, William A. Rogers, Thomas M. Williams

Biology Faculty Publications

Gene expression patterns are specified by cis-regulatory element (CRE) sequences, which are also called enhancers or cis-regulatory modules. A typical CRE possesses an arrangement of binding sites for several transcription factor proteins that confer a regulatory logic specifying when, where, and at what level the regulated gene(s) is expressed. The full set of CREs within an animal genome encodes the organism′s program for development¹, and empirical as well as theoretical studies indicate that mutations in CREs played a prominent role in morphological evolution^2-4. Moreover, human genome wide association studies indicate that genetic variation in CREs …

Laboratory Diagnosis Of Clostridium Difficile Infection: Can Molecular Amplification Methods Move Us Out Of Uncertainty?, Fred C. Tenover, Ellen Jo Baron, Lance R. Peterson, David Persing

Biology Faculty Publications

The laboratory diagnosis of Clostridium difficile infection (CDI) continues to be challenging. Recent guidelines from professional societies in the United States note that enzyme immunoassays for toxins A and B do not have adequate sensitivity to be used alone for detecting CDI, yet the optimal method for diagnosing this infection remains unclear. Nucleic acid amplification tests (NAATs) that target chromosomal toxin genes (usually the toxin B gene, tcdB) show high sensitivity and specificity, provide rapid results, and are amenable to both batch and on-demand testing, but these tests were not universally recommended for routine use in the recent guidelines. …

Activation Of Jnk Signaling Mediates Amyloid-Ss- Dependent Cell Death, Meghana Tare, Rohan Modi, Jaison Nainaparampil, Oorvashi Roy Puli, Shimpi Bedi, Pedro Fernandez-Funez, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Background: Alzheimer's disease (AD) is an age related progressive neurodegenerative disorder. One of the reasons for Alzheimer's neuropathology is the generation of large aggregates of Aß42 that are toxic in nature and induce oxidative stress, aberrant signaling and many other cellular alterations that trigger neuronal cell death. However, the exact mechanisms leading to cell death are not clearly understood.

Methodology/Principal Findings: We employed a Drosophila eye model of AD to study how Aß42 causes cell death. Misexpression of higher levels of Aß42 in the differentiating photoreceptors of fly retina rapidly induced aberrant cellular phenotypes and cell death. We found that …

Mechanical Test Methods For Assessing Porcine Carotid And Uterine Artery Burst Pressure Following Ex Vivo Ultrasonic Ligature Seal And Transection, Carissa M. Krane, Margaret Pinnell, Courtney Gardner, Mercedes Thompson, James Coleman, Robert Wilkens

Biology Faculty Publications

A test method was developed to identify those variables important for assessing the performance of ultrasonic surgical devices in ex vivo ligature sealing of porcine carotid and uterine arteries. Ruggedness testing using a small sample size in pilot experiments was conducted using a newly developed test method in an effort to assess the usefulness of this methodology and to identify test variables that might warrant further testing. The development of this test method included the use of a custom-designed prototypic tension device for load-controlled ex vivo vessel stretching during saline perfusion and subsequent seal and transection of porcine arteries with …

Design Of A Factorial Experiment With Randomization Restrictions To Assess Medical Device Performance On Vascular Tissue, Wiebke Diestelkamp, Carissa M. Krane, Margaret Pinnell

Biology Faculty Publications

Background: Energy-based surgical scalpels are designed to efficiently transect and seal blood vessels using thermal energy to promote protein denaturation and coagulation. Assessment and design improvement of ultrasonic scalpel performance relies on both in vivo and ex vivo testing. The objective of this work was to design and implement a robust, experimental test matrix with randomization restrictions and predictive statistical power, which allowed for identification of those experimental variables that may affect the quality of the seal obtained ex vivo.

Methods: The design of the experiment included three factors: temperature (two levels); the type of solution used to perfuse the …

Endo-Porter–Mediated Delivery Of Phosphorodiamidate Morpholino Oligos (Pmos) In Erythrocyte Suspension Cultures From Cope's Gray Treefrog Hyla Chrysoscelis, Venkateshwar Mutyam, Matthew V. Puccetti, James Frisbie, David L. Goldstein, Carissa M. Krane

Biology Faculty Publications

Cope's gray treefrog, Hyla chrysoscelis, is a freeze-tolerant anuran that accumulates cryoprotective glycerol during cold acclimation. H. chrysoscelis erythrocytes express the aquaglyceroporin HC-3, which facilitates transmembrane glycerol and water movement. Aquaglyceroporins have no pharmacological inhibitors, and no genetic knockout tools currently exist for H. chrysoscelis. A phosphorodiamidate morpholino oligo (PMO)–mediated expression knockdown approach was therefore pursued to provide a model for testing the role of HC-3. We describe a novel procedure optimized for specific, efficient knockdown of HC-3 expression in amphibian erythrocyte suspensions cultured at nonmammalian physiological temperatures using Endo-Porter. Our protocol includes three critical components: pre-incubation at 37°C, …

Dorsal Eye Selector Pannier (Pnr) Suppresses The Eye Fate To Define Dorsal Margin Of The Drosophila Eye, Sarah M. Oros, Meghana Tare, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Axial patterning is crucial for organogenesis. During Drosophila eye development, dorso-ventral (DV) axis determination is the first lineage restriction event. The eye primordium begins with a default ventral fate, on which the dorsal eye fate is established by expression of the GATA-1 transcription factor pannier (pnr). Earlier, it was suggested that loss of pnr function induces enlargement in the dorsal eye due to ectopic equator formation. Interestingly, we found that in addition to regulating DV patterning, pnr suppresses the eye fate by downregulating the core retinal determination genes eyes absent (eya), sine oculis (so) and dacshund (dac) to define the …

Drosophila Adult Eye Model To Teach Scanning Electron Microscopy In An Undergraduate Cell Biology Laboratory, Meghana Tare, Oorvashi Roy Puli, Sarah M. Oros, Amit Singh

Biology Faculty Publications

We have devised an undergraduate laboratory exercise to study tissue morphology using fruit fly, Drosophila melanogaster, as the model organism. Drosophila can be reared in a cost effective manner in a short period of time. This experiment was a part of the undergraduate curriculum of the cell biology laboratory course aimed to demonstrate the use of scanning electron microscopy (SEM) technique to study the morphology of adult eye of Drosophila. The adult eye of Drosophila is a compound eye, which comprises of 800 unit eyes, and serves as an excellent model for SEM studies. We used flies that …

Rapid Evolution Of Sex-Pheromone-Producing Enzyme In Drosophila, Troy R. Shirangi, Héloïse D. Dufour, Thomas M. Williams, Sean B. Carroll

Biology Faculty Publications

A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We …

Altered Regulation Of Aquaporin Gene Expression In Allergen And Il-13-Induced Mouse Models Of Asthma, Carissa M. Krane, Bijia Deng, Venkateshwar Mutyam, Casey A. Mcdonald, Stephen Pazdziorko, Lawrence Mason, Samuel Goldman, Marion Kasaian, Divya Chaudhary, Cara Williams, Melisa W.Y. Ho

Biology Faculty Publications

IL-13 is known to affect many processes that contribute to an asthmatic phenotype, including inflammation, fibrosis, and mucus production. Members of the aquaporin (AQP) family of transmembrane water channels are targets of regulation in models of lung injury and inflammation. Therefore, we examined AQP mRNA and protein expression in allergen and IL-13-induced mouse models of asthma. Lungs from ovalbumin sensitized and ovalbumin challenged (OVA/OVA) and IL-13 treated mice showed airway thickening, increased mucus production, and pulmonary eosinophilia. Pulmonary function tests showed a significant increase in methacholine-induced airway hyperreactivity in OVA/OVA and IL-13-treated mice as compared with controls. Quantitative PCR analysis …

In Vitro Studies On Metabolism Of Salvinorin A, Lukasz M. Kutrzeba, Vardan T. Karamyan, Robert C. Speth, John S. Williamson, Jordan K. Zjawiony

Office for Research Publications and Presentations

Microbial transformation of natural products is a well established model for mammalian metabolism. Salvinorin A, a diterpenoid isolated from the hallucinogenic mint Salvia divinorum Epling & Játiva-M (Lamiaceae), is a potent non-nitrogenous κ-opioid receptor agonist. The metabolism of salvinorin A has still not yet been well established. Thirty fungal species were screened for the ability to metabolize salvinorin A. We observed that salvinorin A undergoes fast hydrolysis of the acetate group at carbon atom C2, resulting in formation of the pharmacologically inactive product, salvinorin B. Ex vivo experiments were also performed using organelle fractions isolated from rat liver and brain. …

Patterning Defects In Silkworm Embryos Analysed Through Cuticle Preparations, Amit Singh, Madhuri Kango-Singh, K. P. Gopinathan

Biology Faculty Publications

The mulberry silkworm, Bombyx mori, a holometabolous lepidopteran insect, has a metameric body plan. Due to its functional adaptation, B. mori presents some unique deviations in its pal/ern from the evolutionarily advanced dipteran insect, Drosophila melanogaster. Previous studies on mutant phenotype analysis in B. mori have been carried out in late stages of larval development. Here we employ, the cuticle preparation approach during embryonic development to study morphological landmarks associated with B. mori, Eri, another race a/silkworm, and pattern defects associated with Ekp mutant of B.mori. The homeotic mutant Ekp, generates ectopic abdominallegs, a feature …

A Cell Biology Laboratory Exercise To Study Sub-Cellular Organelles In Drosophila, Meghana Tare, Amit Singh

Biology Faculty Publications

The fast-changing scenario of undergraduate education puts emphasis on introducing students to hands-on techniques as part of their laboratory courses. In order to cater to large numbers of students and the time constraints involved with undergraduate level laboratory courses, there is a need for development of experiments that are cost effective and can be completed in a defined time frame. We have devised a laboratory exercise for teaching cell biology using the Drosophila melanogaster model. Drosophila can be reared in a short period of time in a cost effective manner. We used Drosophila tissue to study the sub-cellular organization of …

Comparative Functional Analysis Of Aquaporins/Glyceroporins In Mammals And Anurans, Carissa M. Krane, David L. Goldstein

Biology Faculty Publications

Maintenance of fluid homeostasis is critical to establishing and maintaining normal physiology. The landmark discovery of membrane water channels (aquaporins; AQPs) ushered in a new area in osmoregulatory biology that has drawn from and contributed to diverse branches of biology, from molecular biology and genomics to systems biology and evolution, and from microbial and plant biology to animal and translational physiology. As a result, the study of AQPs provides a unique and integrated backdrop for exploring the relationships between genes and genome systems, the regulation of gene expression, and the physiologic consequences of genetic variation. The wide species distribution of …

The Fat Cadherin Acts Through The Hippo Tumor-Suppressor Pathway To Regulate Tissue Size, Maria Willecke, Fisun Hamaratoglu, Madhuri Kango-Singh, Ryan Udan, Chiao-Lin Chen, Chunyao Tao, Xinwei Zhang, Georg Halder

Biology Faculty Publications

Background: The Hippo tumor-suppressor pathway has emerged as a key signaling pathway that controls tissue size in Drosophila. Merlin, the Drosophila homolog of the human Neurofibromatosis type-2 (NF2) tumor-suppressor gene, and the related protein Expanded are the most upstream components of the Hippo pathway identified so far. However, components acting upstream of Expanded and Merlin, such as transmembrane receptors, have not yet been identified.

Results: Here, we report that the protocadherin Fat acts as an upstream component in the Hippo pathway. Fat is a known tumor-suppressor gene in Drosophila, and fat mutants have severely overgrown imaginal discs. We …

Lobe And Serrate Are Required For Cell Survival During Early Eye Development In Drosophila, Amit Singh, Xiao Shi, Kwang-Wook Choi

Biology Faculty Publications

Organogenesis involves an initial surge of cell proliferation, leading to differentiation. This is followed by cell death in order to remove extra cells. During early development, there is little or no cell death. However, there is a lack of information concerning the genes required for survival during the early cell-proliferation phase. Here, we show that Lobe (L) and the Notch (N) ligand Serrate (Ser), which are both involved in ventral eye growth, are required for cell survival in the early eye disc. We observed that the loss-of-ventral-eye phenotype in L or Ser mutants is due to …

Expression Of The Primary Carbohydrate Component Of The Bordetella Bronchiseptica Biofilm Matrix Is Dependent On Growth Phase But Independent Of Bvg Regulation, Yasuhiko Irie, Andrew Preston, Ming H. Yuk

Biology Faculty Publications

We previously showed that the Bvg virulence control system regulates biofilm formation in Bordetella bronchiseptica (Y. Irie, S. Mattoo, and M. H. Yuk, J. Bacteriol. 186:5692-5698, 2004). Analyses of the extracellular components of B. bronchiseptica biofilm matrix revealed that the major sugar component in the matrix was xylose, and linkage analysis indicated a majority of it to be in a 4-linked polymeric form. The production of xylose was independent of Bvg regulation but instead was dependent on bacterial growth phase. In addition, N-acetyl-glucosamine in the matrix was found to be important for the initial development of the biofilm. These …

Eye Development At The Houston "Fly Meeting", Amit Singh

Biology Faculty Publications

Meeting report: The 47th Annual Drosophila Research Conference or "Fly Meeting" took place at Houston, Texas, USA from March 29th- April 2nd, 2006, under the aegis of the Genetics Society of America. The Fly Meeting provides an excellent opportunity for fly researchers to present their work and to get a snapshot of recent developments and upcoming trends in their research field. The fruit fly, Drosophila melanogaster, is a very versatile model to study growth, patterning, neural development, evolution, systemetics and various other facets of biomedical science. The topics presented in the meeting covered a very broad spectrum of fly research. …

Empirical Analysis Of The Str Profiles Resulting From Conceptual Mixtures, David R. Paoletti, Travis E. Doom, Carissa M. Krane, Michael L. Raymer, Dan E. Krane

Biology Faculty Publications

Samples containing DNA from two or more individuals can be difficult to interpret. Even ascertaining the number of contributors can be challenging and associated uncertainties can have dramatic effects on the interpretation of testing results. Using an FBI genotypes dataset, containing complete genotype information from the 13 Combined DNA Index System (CODIS) loci for 959 individuals, all possible mixtures of three individuals were exhaustively and empirically computed. Allele sharing between pairs of individuals in the original dataset, a randomized dataset and datasets of generated cousins and siblings was evaluated as were the number of loci that were necessary to reliably …

Atypical Pkciota Contributes To Poor Prognosis Through Loss Of Apical-Basal Polarity And Cyclin E Overexpression In Ovarian Cancer, Astrid M. Eder, Xiaomei Sui, Daniel G. Rosen, Laura K. Nolden, Kwai Wa Cheng, John P. Lahad, Madhuri Kango-Singh, Karen H. Lu, Carla L. Warneke, Edward N. Atkinson, Isabelle Bedrosian, Khandan Keyomarsi, Wen-Lin Kuo, Joe W. Gray, Jerry C. P. Yin, Jinsong Liu, Georg Halder, Gordon B. Mills

Biology Faculty Publications

We show that atypical PKCι, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCι protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCι DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCι proteins levels are associated with …