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Transcriptional And Post-Transcriptional Regulation Of Histone Variant H2a.Z During Sea Urchin Development, Mihai Hajdu 2017 The Graduate Center, City University of New York

Transcriptional And Post-Transcriptional Regulation Of Histone Variant H2a.Z During Sea Urchin Development, Mihai Hajdu

All Graduate Works by Year: Dissertations, Theses, and Capstone Projects

Histone variant H2A.Z promotes chromatin accessibility at transcriptional regulatory elements and is developmentally regulated in metazoans. We characterize the transcriptional and post-transcriptional regulation of H2A.Z in the purple sea urchin Strongylocentrotus purpuratus. H2A.Z depletion by antisense translation-blocking morpholino oligonucleotides during early development causes developmental collapse, in agreement with its previously demonstrated general role in transcriptional multipotency. During H2A.Z peak expression in 24-h embryos, endogenous H2A.Z 3’ UTR sequences stabilize GFP mRNAs relative to those with SV40 3’ UTR sequences, although the 3’UTR of H2A.Z does not determine the spatial distribution of H2A.Z ...


Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith 2017 Old Dominion University

Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived ...


Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski 2016 University of Massachusetts Medical School

Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski

GSBS Dissertations and Theses

Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational ...


Sirt1 Regulates Glial Progenitor Proliferation And Regeneration In White Matter After Neonatal Brain Injury., Beata Jablonska, Marcin Gierdalski, Li-Jin Chew, Teresa Hawley, Mackenzie Catron, Arturo Lichauco, Juan Cabrera-Luque, Tracy Yuen, David Rowitch, Vittorio Gallo 2016 George Washington University

Sirt1 Regulates Glial Progenitor Proliferation And Regeneration In White Matter After Neonatal Brain Injury., Beata Jablonska, Marcin Gierdalski, Li-Jin Chew, Teresa Hawley, Mackenzie Catron, Arturo Lichauco, Juan Cabrera-Luque, Tracy Yuen, David Rowitch, Vittorio Gallo

Pediatrics Faculty Publications

Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown ...


Retinoic Acid Signaling Regulates Krt5 Independently Of Stem Cell Markers In Submandibular Salivary Gland Epithelium., Timur Maratovich Abashev 2016 University of Louisville

Retinoic Acid Signaling Regulates Krt5 Independently Of Stem Cell Markers In Submandibular Salivary Gland Epithelium., Timur Maratovich Abashev

Electronic Theses and Dissertations

Vitamin A metabolism, which produces the signaling molecule Retinoic Acid (RA), has been demonstrated to be important for growth and branching morphogenesis of mammalian embryonic salivary gland epithelium. However, it is not known whether RA functions directly within epithelial cells or in associated tissues that influence morphogenesis of salivary epithelium. Moreover, downstream targets of RA transcriptional regulation have not been identified. Here we show that canonical RA signaling occurs in multiple tissues of embryonic mouse salivary glands, including epithelium, associated parasympathetic ganglion neurons, and non‑neuronal mesenchyme. By culturing epithelium explants in isolation from other tissues we demonstrate that RA ...


Rna Sequencing Analysis Of The Developing Chicken Retina, Christophe Langouet-Astrie*, Annamarie Meinsen*, Emily R. Grunwald*, Stephen Turner, Raymond A. Enke 2016 James Madison University

Rna Sequencing Analysis Of The Developing Chicken Retina, Christophe Langouet-Astrie*, Annamarie Meinsen*, Emily R. Grunwald*, Stephen Turner, Raymond A. Enke

Ray Enke Ph.D.

RNA sequencing transcriptome analysis using massively parallel next generation sequencing technology provides the capability to understand global changes in gene expression throughout a range of tissue samples. Development of the vertebrate retina requires complex temporal orchestration of transcriptional activation and repression. The chicken embryo (Gallus gallus) is a classic model system for studying developmental biology and retinogenesis. Existing retinal transcriptome projects have been critical to the vision research community for studying aspects of murine and human retinogenesis, however, there are currently no publicly available data sets describing the developing chicken retinal transcriptome. Here we used Illumina RNA sequencing (RNA-seq) analysis ...


Transient Runx1 Expression During Early Mesendodermal Differentiation Of Hescs Promotes Epithelial To Mesenchymal Transition Through Tgfb2 Signaling, Jennifer J. VanOudenhove, Ricardo F. Medina, Prachi N. Ghule University of Vermont College of Medicine, Jane B. Lian, Janet L. Stein, Sayyed K. Zaidi, Gary S. Stein 2016 University of Massachusetts Medical School

Transient Runx1 Expression During Early Mesendodermal Differentiation Of Hescs Promotes Epithelial To Mesenchymal Transition Through Tgfb2 Signaling, Jennifer J. Vanoudenhove, Ricardo F. Medina, Prachi N. Ghule University Of Vermont College Of Medicine, Jane B. Lian, Janet L. Stein, Sayyed K. Zaidi, Gary S. Stein

Open Access Articles

The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of repression for several epithelial genes, indicating that loss of RUNX1 impaired an epithelial to mesenchymal transition during differentiation. Cell ...


Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes 2016 Universidade do Porto - Portugal

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes

Stephen O'Brien

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we used comparative genomic and adaptive evolutionary analyses to ...


Associations Of Peripubertal Serum Dioxin And Polychlorinated Biphenyl Concentrations With Pubertal Timing Among Russian Boys, Jane S. Burns, Mary M. Lee, Paige L. Williams, Susan A. Korrick, Oleg Sergeyev, Thuy Lam, Boris Revich, Russ Hauser 2016 Harvard School of Public Health

Associations Of Peripubertal Serum Dioxin And Polychlorinated Biphenyl Concentrations With Pubertal Timing Among Russian Boys, Jane S. Burns, Mary M. Lee, Paige L. Williams, Susan A. Korrick, Oleg Sergeyev, Thuy Lam, Boris Revich, Russ Hauser

Mary M. Lee

BACKGROUND: Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and nondioxin-like, have been linked to alterations in puberty. OBJECTIVES: We examined the association of peripubertal serum levels of these compounds (and their toxic equivalents (TEQs)) with pubertal onset and maturity among Russian boys enrolled at ages 8-9 years and followed prospectively through ages 17-18 years. METHODS: At enrollment, 473 boys had serum dioxin-like compounds and PCBs measured. At the baseline visit and annually until age 17-18 years, a physician performed pubertal staging [Genitalia (G), Pubarche (P), and testicular volume (TV)]. 315 subjects completed the follow-up visit at 17-18 years of age ...


A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page 2016 Whitehead Institute

A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page

Open Access Articles

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells ...


Regulation Of X-Linked Gene Expression During Early Mouse Development By Rlim, Feng Wang, JongDae Shin, Jeremy Shea, Jun Yu, Ana Boskovic, Meg Byron, Xiaochun Zhu, Alex K. Shalek, Aviv Regev, Jeanne B. Lawrence, Eduardo M. Torres, Lihua J. Zhu, Oliver J. Rando, Ingolf Bach 2016 University of Massachusetts Medical School

Regulation Of X-Linked Gene Expression During Early Mouse Development By Rlim, Feng Wang, Jongdae Shin, Jeremy Shea, Jun Yu, Ana Boskovic, Meg Byron, Xiaochun Zhu, Alex K. Shalek, Aviv Regev, Jeanne B. Lawrence, Eduardo M. Torres, Lihua J. Zhu, Oliver J. Rando, Ingolf Bach

Open Access Articles

Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our ...


Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan 2016 University of Birmingham

Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan

Molecular, Cell and Cancer Biology Publications

BACKGROUND: ATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Apoptosis-induced proliferation (AiP) is a caspase-directed and JNK-dependent process which is involved in tissue repair and regeneration after massive stress-induced apoptotic cell loss. Under certain conditions, AiP can cause tissue overgrowth with implications for cancer.

RESULTS: Here, we show that Atg1 in Drosophila (dAtg1) has a previously unrecognized function for both regenerative and overgrowth-promoting AiP in eye and wing imaginal discs. dAtg1 acts genetically downstream of and is transcriptionally induced by JNK activity, and it is required ...


Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager 2016 University of Wisconsin-La Crosse

Modeling And Analysis Of Germ Layer Formations Using Finite Dynamical Systems, Alexander Garza, Megan Eberle, Eric A. Eager

Spora: A Journal of Biomathematics

The development of an embryo from a fertilised egg to a multicellular organism proceeds through numerous steps, with the formation of the three germ layers (endoderm, mesoderm, ectoderm) being one of the first. In this paper we study the mesendoderm (the tissue that collectively gives rise to both mesoderm and endoderm) gene regulatory network for two species, \textit{Xenopus laevis} and the axolotl (\textit{Ambystoma mexicanum}) using Boolean networks. We find that previously-established bistability found in these networks can be reproduced using this Boolean framework, provided that some assumptions used in previously-published differential equations models are relaxed. We conclude by ...


Septate Junction Proteins Play Essential Roles In Morphogenesis Throughout Embryonic Development In Drosophila, Sonia Hall, Robert E. Ward 4th 2016 University of Massachusetts Medical School

Septate Junction Proteins Play Essential Roles In Morphogenesis Throughout Embryonic Development In Drosophila, Sonia Hall, Robert E. Ward 4th

Open Access Articles

The septate junction (SJ) is the occluding junction found in the ectodermal epithelia of invertebrate organisms, and is essential to maintain chemically distinct compartments in epithelial organs, to provide the blood-brain barrier in the nervous system, and to provide an important line of defense against invading pathogens. More than 20 genes have been identified to function in the establishment or maintenance of SJs in Drosophila melanogaster Numerous studies have demonstrated the cell biological function of these proteins in establishing the occluding junction, whereas very few studies have examined further developmental roles for them. Here we examined embryos with mutations in ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis 2016 University of Massachusetts Medical School

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez 2016 The University of Texas Graduate School of Biomedical Sciences at Houston

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

UT GSBS Dissertations and Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found ...


Morpholino-Mediated Knockdown Of Dux4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics, Jennifer C. J. Chen, Oliver D. King, Yuanfan Zhang, Nicholas P. Clayton, Carrie Spencer, Bruce M. Wentworth, Charles P. Emerson Jr., Kathryn R. Wagner 2016 University of Massachusetts Medical School

Morpholino-Mediated Knockdown Of Dux4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics, Jennifer C. J. Chen, Oliver D. King, Yuanfan Zhang, Nicholas P. Clayton, Carrie Spencer, Bruce M. Wentworth, Charles P. Emerson Jr., Kathryn R. Wagner

Cell and Developmental Biology Publications and Presentations

Derepression of DUX4 in skeletal muscle has emerged as a likely cause of pathology in facioscapulohumeral muscular dystrophy (FSHD). Here we report on the use of antisense phosphorodiamidate morpholino oligonucleotides to suppress DUX4 expression and function in FSHD myotubes and xenografts. The most effective was phosphorodiamidate morpholino oligonucleotide FM10, which targets the polyadenylation signal of DUX4. FM10 had no significant cell toxicity, and RNA-seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects. Electroporation of FM10 into FSHD patient muscle xenografts in mice also down-regulated DUX4 and DUX4 targets. These ...


Dichotomous Key To Pea Aphid (Acyrthosiphon Pisum) Apterous Parthenogenic Instars, Bates College Department of Biology, Daisy Diamond, Daniel Levitis 2016 Bates College

Dichotomous Key To Pea Aphid (Acyrthosiphon Pisum) Apterous Parthenogenic Instars, Bates College Department Of Biology, Daisy Diamond, Daniel Levitis

SCARAB Data Repository

We provide a dichotomous key, with photographs and illustrations, for distinguishing between instars of the pea aphid (Acyrthosiphon pisum) in the developmental pathway leading to the apterous parthenogenetic adult. Lengths of body, antenna and cauda are provided for a sample of each instar.


A Usp28-53bp1-P53-P21 Signaling Axis Arrests Growth After Centrosome Loss Or Prolonged Mitosis, Bramwell G. Lambrus, Vikas Daggubati, Yumi Uetake, Phillip M. Scott, Kevin M. Clutario, Greenfield Sluder, Andrew J. Holland 2016 Johns Hopkins University School of Medicine

A Usp28-53bp1-P53-P21 Signaling Axis Arrests Growth After Centrosome Loss Or Prolonged Mitosis, Bramwell G. Lambrus, Vikas Daggubati, Yumi Uetake, Phillip M. Scott, Kevin M. Clutario, Greenfield Sluder, Andrew J. Holland

Cell and Developmental Biology Publications and Presentations

Precise regulation of centrosome number is critical for accurate chromosome segregation and the maintenance of genomic integrity. In nontransformed cells, centrosome loss triggers a p53-dependent surveillance pathway that protects against genome instability by blocking cell growth. However, the mechanism by which p53 is activated in response to centrosome loss remains unknown. Here, we have used genome-wide CRISPR/Cas9 knockout screens to identify a USP28-53BP1-p53-p21 signaling axis at the core of the centrosome surveillance pathway. We show that USP28 and 53BP1 act to stabilize p53 after centrosome loss and demonstrate this function to be independent of their previously characterized role in ...


Supervillin Is A Component Of The Hair Cell's Cuticular Plate And The Head Plates Of Organ Of Corti Supporting Cells, Lana M. Pollock, Nilay Gupta, Xi Chen, Elizabeth J. Luna, Brian M. McDermott Jr 2016 Case Western Reserve University

Supervillin Is A Component Of The Hair Cell's Cuticular Plate And The Head Plates Of Organ Of Corti Supporting Cells, Lana M. Pollock, Nilay Gupta, Xi Chen, Elizabeth J. Luna, Brian M. Mcdermott Jr

Cell and Developmental Biology Publications and Presentations

The organ of Corti has evolved a panoply of cells with extraordinary morphological specializations to harness, direct, and transduce mechanical energy into electrical signals. Among the cells with prominent apical specializations are hair cells and nearby supporting cells. At the apical surface of each hair cell is a mechanosensitive hair bundle of filamentous actin (F-actin)-based stereocilia, which insert rootlets into the F-actin meshwork of the underlying cuticular plate, a rigid organelle considered to hold the stereocilia in place. Little is known about the protein composition and development of the cuticular plate or the apicolateral specializations of organ of Corti ...


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