Life Sciences Commons^™

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

Madhuri Kango-Singh

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 …

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

Madhuri Kango-Singh

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 …

Eye Suppression, A Novel Function Of Teashirt, Requires Wingless Signaling, Amit Singh, Madhuri Kango-Singh, Y. Henry Sun

Madhuri Kango-Singh

Teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has been shown to induce ectopic eye formation in the antenna. We report that tsh can suppress eye development. This novel function of tsh is due to the induction of homothorax (hth), a known repressor of eye development, and requires Wingless (WG) signaling. Interestingly, tsh has different functions in the dorsal and ventral eye, suppressing eye development close to the ventral margin, while promoting eye development near the dorsal margin. It affects both growth of eye disc and retinal cell differentiation.

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

Madhuri Kango-Singh

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, due …

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

Madhuri Kango-Singh

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 …

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

Madhuri Kango-Singh

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 …

An Improved Method For Chemical Devitellinization Of X-Gal Stained Drosophila Embryos, Amit Singh, Madhuri Kango-Singh, P. Sinha

Madhuri Kango-Singh

In Drosophila developmental biological studies, X-gal staining is commonly employed to study the spatio-temporal expression of the lacZ reporter gene in the transformed flies or their embryos. Study of the lacZ pattern in embryos often suffers from the lack of an efficient and high yieldirrg technique for devitellinization of X-gal stained embryos. Devitellinization techniques employed during antibody staining, in situ hybridization or embryonic cuticular preparations generally do not give satisfactory results when used for similar purpose in X-gal stained embryos. This results in the flaky appearance of the blue stain. We present here an improved chemical devitellinization technique which gives …

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

Madhuri Kango-Singh

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 …

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

Madhuri Kango-Singh

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 found that …