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2014

Genetics

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Articles 1 - 26 of 26

Full-Text Articles in Cell Biology

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan Dec 2014

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq ...


Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan Dec 2014

Understanding The Meiotic Roles Of Sisters Unbound In Drosophila Melanogaster, Badri Krishnan

Doctoral Dissertations

During meiosis, cohesin is required for sister chromatid cohesion and for formation of chromosome cores. Multiple processes including chromosome segregation, recombination and synaptonemal complex (SC) are dependent on cohesin. Cohesin complex consists of two SMC subunits- SMC1, SMC3 and two non-SMC subunits RAD21/REC8 in meiosis and SA. But in Drosophila, non-SMC subunits have not been shown to be required for cohesion. We have identified a gene sisters unbound, which along with previously identified ord and solo, form a group of three genes (sos) which do not have any sequence similarity to cohesins but performs functions demonstrated by cohesins.

Proper ...


Optimization Of Transcription Factor Binding Map Accuracy Utilizing Knockout-Mouse Models, Wolfgang Krebs, Susanne V. Schmidt, Alon Goren, Dominic De Nardo, Larisa Labzin, Anton Bovier, Thomas Ulas, Heidi Theis, Michael Kraut, Eicke Latz, Marc Beyer, Joachim L. Schultze Dec 2014

Optimization Of Transcription Factor Binding Map Accuracy Utilizing Knockout-Mouse Models, Wolfgang Krebs, Susanne V. Schmidt, Alon Goren, Dominic De Nardo, Larisa Labzin, Anton Bovier, Thomas Ulas, Heidi Theis, Michael Kraut, Eicke Latz, Marc Beyer, Joachim L. Schultze

Open Access Articles

Genome-wide assessment of protein-DNA interaction by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key technology for studying transcription factor (TF) localization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq studies depend on many variables, including antibody affinity and specificity. Thus far, efforts to improve antibody reagents for ChIP-seq experiments have focused mainly on generating higher quality antibodies. Here we introduce KOIN (knockout implemented normalization) as a novel strategy to increase signal specificity and reduce noise by using TF knockout mice as a critical control for ChIP-seq data experiments. Additionally, KOIN can identify 'hyper ChIPable ...


Intercellular Cooperation And Competition In Brain Cancers: Lessons From Drosophila And Human Studies, Indrayani Waghmare, Austin Roebke, Mutsuko Minata, Madhuri Kango-Singh, Ichiro Nakano Nov 2014

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 ...


Genetic Analysis Of Ton2 Dependent Processes In Microtubule Organization In Arabidopsis Thaliana, Samantha Nicole Atkinson Oct 2014

Genetic Analysis Of Ton2 Dependent Processes In Microtubule Organization In Arabidopsis Thaliana, Samantha Nicole Atkinson

Theses and Dissertations

Microtubules carry out many functions within the cell. They're used during mitosis and meiosis to move chromosomes to opposite sides of the cell so that cell division can occur. They're also used as structural support for the cell and are involved in establishing the cell shape. Microtubules are also able to reorient from a longitudinal orientation to a transverse orientation in response to gibberellic acid and auxin (two hormones that are involved in cell elongation). The mechanism for how this reorientation occurs is unknown. The TONNEAU2 (TON2) protein is necessary for proper microtubule organization. We looked at how ...


Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad Oct 2014

Associated Behavioral, Genetic, And Gene Expression Variation With Alternative Life History Tactics In Salmonid Fishes, Ashley Chin-Baarstad

Open Access Dissertations

Individual differences in behavior can have potential fitness consequences and often reflect underlying genetic variation. My research focuses on three objectives related to individual level variation: 1) evaluating the innate behavioral variation within and between individuals, families, and progeny of different life-history types across time; 2) testing for differences in gene expression within the brain associated with this behavioral variation; and 3) using genetic polymorphisms to test for associations with ecotype, as well as population structure, in polymorphic populations. First, we evaluated the variation in a suite of ecologically relevant behaviors across time in juvenile progeny produced from crosses within ...


Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine Sep 2014

Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine

GSBS Dissertations and Theses

During each life cycle, gametes must preserve and pass on both genetic and epigenetic information, making the germline both immortal and totipotent. In the male germline the dramatic morphological transformation of a germ cell through meiosis, into a sperm competent for fertilization, while retaining this information is an incredible example of cellular differentiation. This process of spermatogenesis is inherently thermosensitive in numerous metazoa ranging from worms to man. Here, I describe the role of two redundant AGO-class paralogs, ALG-3/4, and their small RNA cofactors, in promoting thermotolerant male fertility in Caenorhabditis elegans. alg-3/4 double mutants exhibit temperature dependent ...


A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando Aug 2014

A System For Genome-Wide Histone Variant Dynamics In Es Cells Reveals Dynamic Macroh2a2 Replacement At Promoters, Ozlem Yildirim, Jui-Hung Hung, Ryan J. Cedeno, Zhiping Weng, Christopher J. Lengner, Oliver J. Rando

Open Access Articles

Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states, chromatin insulator function, chromosome folding, and the maintenance of the pluripotent state of embryonic stem cells. Here, we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues, recapitulating expected characteristics of the well characterized H3.3 histone variant. We extended this system to the less-studied MacroH2A2 variant, commonly described as a "repressive" histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated ...


Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang Aug 2014

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important ...


Cellular Contractility And Extracellular Matrix Stiffness Regulate Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Haage, Ian C. Schneider Aug 2014

Cellular Contractility And Extracellular Matrix Stiffness Regulate Matrix Metalloproteinase Activity In Pancreatic Cancer Cells, Amanda Haage, Ian C. Schneider

Chemical and Biological Engineering Publications

The pathogenesis of cancer is often driven by local invasion and metastasis. Recently, mechanical properties of the tumor microenvironment have been identified as potent regulators of invasion and metastasis, while matrix metalloproteinases (MMPs) are classically known as significant enhancers of cancer cell migration and invasion. Here we have been able to sensitively measure MMP activity changes in response to specific extracellular matrix (ECM) environments and cell contractility states. A pancreatic cancer cell line, Panc-1 cells, up-regulate MMP activities between 3- and 10- fold with increased cell contractility. Conversely, they down-regulate MMP activities when contractility is blocked to levels seen with ...


Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco Jul 2014

Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco

Rev. Nicanor Austriaco, O.P.

Pioneered by companies like 23andMe.com, deCODEme.com, and Navigenics.com, direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print media, or the Internet. This kind of testing provides access to a customer’s genetic information without necessarily involving either a medical health care professional or a genetic counselor in the process. In recent years, a course offered to medical and graduate students at Stanford University has included an option for students to undergo personal genotyping, raising the possibility that direct-to-consumer genetic testing could also be incorporated into undergraduate biology courses to enhance ...


Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park Jul 2014

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated ...


Functional Study Of The Suppressor Of Hairy-­Wing Insulator Protein In Drosophila Melanogaster, Shih-Jui Hsu May 2014

Functional Study Of The Suppressor Of Hairy-­Wing Insulator Protein In Drosophila Melanogaster, Shih-Jui Hsu

Doctoral Dissertations

Eukaryotic chromatin insulators play an essential role in regulating gene expression and modifying nuclear architecture by organizing the higher-order chromatin structure in response to cellular and developmental cues. The details on how insulators function in this capacity are not completely understood.

Five different types of insulators have been identified in Drosophila. Each functional insulator consists of an insulator DNA response element bound by an insulator protein, which recognizes specific DNA sequences. Each type of insulator functions individually as well as collaboratively. Except for the Su(Hw) insulator protein, the other insulator proteins are necessary for viability considering loss of Su ...


The Number Of Lines A Cell Contacts And Cell Contractility Drive The Efficiency Of Contact Guidance, Nicholas R. Romsey, Yue Hou, Laura L. Rodriguez, Ian C. Schneider Mar 2014

The Number Of Lines A Cell Contacts And Cell Contractility Drive The Efficiency Of Contact Guidance, Nicholas R. Romsey, Yue Hou, Laura L. Rodriguez, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell migration is an important biological function that impacts many physiological and pathological processes. Often migration is directed along various densities of aligned fibers of collagen, a process called contact guidance. However, cells adhere to other components in the extracellular matrix, possibly affecting migrational behavior. Additionally, changes in intracellular contractility are well known to affect random migration, but its effect on contact guidance is less known. This study examines differences in directed migration in response to variations in the spacing of collagen, non-specific background adhesion strength and myosin II-mediated contractility. Collagen was microcontact printed onto glass substrates and timelapse live-cell ...


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 Mar 2014

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 ...


Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco Feb 2014

Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco

Biology Department Faculty Publications

Pioneered by companies like 23andMe.com, deCODEme.com, and Navigenics.com, direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print media, or the Internet. This kind of testing provides access to a customer’s genetic information without necessarily involving either a medical health care professional or a genetic counselor in the process. In recent years, a course offered to medical and graduate students at Stanford University has included an option for students to undergo personal genotyping, raising the possibility that direct-to-consumer genetic testing could also be incorporated into undergraduate biology courses to enhance ...


Deletion Of Aif1 But Not Of Yca1/Mca1 Protects Saccharomyces Cerevisiae And Candida Albicans Cells From Caspofungin-Induced Programmed Cell Death, Nicanor Austriaco, Christopher Chin, Faith Donaghey, Kathrine Helming, Morgan Mccarthy, Stephen Rogers Feb 2014

Deletion Of Aif1 But Not Of Yca1/Mca1 Protects Saccharomyces Cerevisiae And Candida Albicans Cells From Caspofungin-Induced Programmed Cell Death, Nicanor Austriaco, Christopher Chin, Faith Donaghey, Kathrine Helming, Morgan Mccarthy, Stephen Rogers

Biology Department Faculty Publications

Caspofungin was the first member of a new class of antifungals called echinocandins to be approved by a drug regulatory authority. Like the other echinocandins, caspofungin blocks the synthesis of β(1,3)-D-glucan of the fungal cell wall by inhibiting the enzyme, β(1,3)-D-glucan synthase. Loss of β(1,3)-D-glucan leads to osmotic instability and cell death. However, the precise mechanism of cell death associated with the cytotoxicity of caspofungin was unclear. We now provide evidence that Saccharomyces cerevisiae cells cultured in media containing caspofungin manifest the classical hallmarks of programmed cell death (PCD) in yeast ...


Genetic Models Of Apoptosis-Induced Proliferation Decipher Activation Of Jnk And Identify A Requirement Of Egfr Signaling For Tissue Regenerative Responses In Drosophila, Yun Fan, Shiuan Wang, Jacob Hernandez, Vildan Betul Yenigun, Gillian Hertlein, Caitlin E. Fogarty, Jillian L. Lindblad, Andreas Bergmann Jan 2014

Genetic Models Of Apoptosis-Induced Proliferation Decipher Activation Of Jnk And Identify A Requirement Of Egfr Signaling For Tissue Regenerative Responses In Drosophila, Yun Fan, Shiuan Wang, Jacob Hernandez, Vildan Betul Yenigun, Gillian Hertlein, Caitlin E. Fogarty, Jillian L. Lindblad, Andreas Bergmann

University of Massachusetts Medical School Faculty Publications

Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been ...


Phosphoregulation Of Sfi1 Is Required For Yeast Centrosome Duplication And Separation, Jennifer Susan Avena Jan 2014

Phosphoregulation Of Sfi1 Is Required For Yeast Centrosome Duplication And Separation, Jennifer Susan Avena

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Centrosomes serve as the main microtubule–organizing centers in many eukaryotic cells. Duplication of centrosomes once per cell cycle is essential for bipolar spindle formation and genome maintenance and requires control by protein kinases, including cyclin–dependent kinases (Cdks). However, an understanding of the mechanisms by which centrosome duplication is regulated and, in particular, restricted to once per cell cycle is still lacking. Sfi1, a conserved component of centrosomes, is a phospho–protein that is a key candidate for establishing the site of new centrosome assembly in the budding yeast Saccharomyces cerevisiae, likely via domain–specific functions. I have examined ...


Loss Of Gq/11 Genes Does Not Abolish Melanopsin Phototransduction, Kylie S. Chew, Tiffany M. Schmidt, Alan C. Rupp, Paulo Kofuji, Jeffrey M. Trimarchi Jan 2014

Loss Of Gq/11 Genes Does Not Abolish Melanopsin Phototransduction, Kylie S. Chew, Tiffany M. Schmidt, Alan C. Rupp, Paulo Kofuji, Jeffrey M. Trimarchi

Genetics, Development and Cell Biology Publications

In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment melanopsin, which renders them intrinsically photosensitive (ipRGCs). These ipRGCs mediate various non-image-forming visual functions such as circadian photoentrainment and the pupillary light reflex (PLR). Melanopsin phototransduction begins with activation of a heterotrimeric G protein of unknown identity. Several studies of melanopsin phototransduction have implicated a G-protein of the Gq/11 family, which consists of Gna11, Gna14, Gnaq and Gna15, in melanopsin-evoked depolarization. However, the exact identity of the Gq/11 gene involved in this process has remained elusive. Additionally, whether Gq/11 G-proteins are necessary for melanopsin phototransduction ...


Collagen Attachment To The Substrate Controls Cell Clustering Through Migration, Yue Hou, Laura L. Rodriguez, Juan Wang, Ian C. Schneider Jan 2014

Collagen Attachment To The Substrate Controls Cell Clustering Through Migration, Yue Hou, Laura L. Rodriguez, Juan Wang, Ian C. Schneider

Chemical and Biological Engineering Publications

Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell-cell junctions. Much less is known about how the ECM regulates cells with weak cell-cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in ...


Starting Small: Transcriptomics With Single And Small Populations Of Cells, Caitlin Farris Jan 2014

Starting Small: Transcriptomics With Single And Small Populations Of Cells, Caitlin Farris

Graduate Theses and Dissertations

Studying the transcriptome of organisms allows for the characterization of different aspects of development and disease progression. Studies of this kind are usually done with large numbers of cells, giving an expression profile that serves as an overview of that cell type or tissue. In this thesis, two different transcriptomic studies were done with small populations of cells and with single cells. To examine the immune response of a hSOD1G93A Amytrophic Lateral Sclerosis (ALS) mouse model, small populations of cells were analyzed by microarray using a protocol modified from one developed by Trimarchi et al (2007) to study single cells ...


Regulation Of Chromosome Segregation In Drosophila Meiosis, Zhi Hao Guo Jan 2014

Regulation Of Chromosome Segregation In Drosophila Meiosis, Zhi Hao Guo

Electronic Theses and Dissertations

Sister-chromatid cohesion is maintained by Cohesin complex. Separase releases the cohesion through the cleavage of the kleisin subunit of Cohesin complex. Separase is regulated by its inhibitor, Securin/Pim. These processes are well studied in mitosis but little is known for meiosis. I found that Separase is required for the proper separation of homologous chromosomes and sister chromatids in Drosophila meiosis. Its function is inhibited by Securin/Pim during the process. I showed that the common kleisin subunit, Rad21, is not likely to be the meiotic target of Separase and that Rad21 and another common Cohesin component, SMC3/CAP, does ...


Live-Cell Imaging Of Pol Ii Promoter Activity To Monitor Gene Expression With Rna Imagetag Reporters, Ilchung Shin, Judhajeet Ray, Vinayak Gupta, Muslum Ilgu, Jonathan Scott Beasley, Lee Bendickson, Samir Mehanovic, George A. Kraus, Marit Nilsen-Hamilton Jan 2014

Live-Cell Imaging Of Pol Ii Promoter Activity To Monitor Gene Expression With Rna Imagetag Reporters, Ilchung Shin, Judhajeet Ray, Vinayak Gupta, Muslum Ilgu, Jonathan Scott Beasley, Lee Bendickson, Samir Mehanovic, George A. Kraus, Marit Nilsen-Hamilton

Biochemistry, Biophysics and Molecular Biology Publications

We describe a ribonucleic acid (RNA) reporter system for live-cell imaging of gene expression to detect changes in polymerase II activity on individual promoters in individual cells. The reporters use strings of RNA aptamers that constitute IMAGEtags (Intracellular MultiAptamer GEnetic tags) that can be expressed from a promoter of choice. For imaging, the cells are incubated with their ligands that are separately conjugated with one of the FRET pair, Cy3 and Cy5. The IMAGEtags were expressed in yeast from the GAL1, ADH1 or ACT1 promoters. Transcription from all three promoters was imaged in live cells and transcriptional increases from the ...


Onecut1 And Onecut2 Play Critical Roles In The Development Of The Mouse Retina, Jillian J. Goetz, Gregory M. Martin, Rebecca Chowdhury, Jeffrey M. Trimarchi Jan 2014

Onecut1 And Onecut2 Play Critical Roles In The Development Of The Mouse Retina, Jillian J. Goetz, Gregory M. Martin, Rebecca Chowdhury, Jeffrey M. Trimarchi

Genetics, Development and Cell Biology Publications

The entire repertoire of intrinsic factors that control the cell fate determination process of specific retinal neurons has yet to be fully identified. Single cell transcriptome profiling experiments of retinal progenitor cells revealed considerable gene expression heterogeneity between individual cells, especially among different classes of transcription factors. In this study, we show that two of those factors, Onecut1 and Onecut2, are expressed during mouse retinal development. Using mice that are deficient for each of these transcription factors, we further demonstrate a significant loss (∼70–80%) of horizontal cells in the absence of either of these proteins, while the other retinal ...


Mutual Reinforcement Between Telomere Capping And Canonical Wnt Pathway Activity In The Intestinal Stem Cell Niche, Ting-Lin Yang Jan 2014

Mutual Reinforcement Between Telomere Capping And Canonical Wnt Pathway Activity In The Intestinal Stem Cell Niche, Ting-Lin Yang

Publicly Accessible Penn Dissertations

Mice lacking telomerase (e.g. mTR-/-) for several generations develop dysfunctional telomeres and severe gastrointestinal pathology. Intestinal stem cell (ISC) abnormalities in late-generation mTR mice have been described, and we set out to characterize it in more detail. Expression profiling of mTR-/- crypts and an unbiased gene set enrichment analysis revealed broadly decreased expression of Wnt pathway genes in crypt epithelia and underlying stroma. We describe abnormalities in the Wnt-dependent intestinal stem cell (ISC) niche in these mice, including decreased expression of ISC marker genes Ascl2, Lgr5, and Sox9. The importance of these changes was revealed by rescue of crypt ...