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Arterial Distribution Of The Human Aorta: An Examination Of The Evolutionary, Developmental, And Physiological Bases Of Asymmetry., Brandon Oddo, Cooker Storm 2019 Pepperdine University

Arterial Distribution Of The Human Aorta: An Examination Of The Evolutionary, Developmental, And Physiological Bases Of Asymmetry., Brandon Oddo, Cooker Storm

Seaver College Research And Scholarly Achievement Symposium

The study of anatomy contends that “form follows function”; a disciplinary theme purporting that anatomical structures (i.e., cells, tissues, and organs) have a shape that serves its proper function. With this in mind, it is unclear why human arterial distribution off the aortic arch is asymmetrical, while the corresponding venous anatomy is symmetrical. We investigated the evolutionary, developmental, and physiological bases for the asymmetry of aortic arch branches in humans. First, we investigated the cardiovascular anatomy of ancestral species to determine if, and at what level, anatomical divergence (from aortic symmetry to asymmetry) occurs. Second, we examined the formation ...


Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas 2019 Harvard Medical School

Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas

Open Access Articles

The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq ...


Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman 2018 University of Massachusetts Medical School

Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery ...


Dynamic Placement Of The Linker Histone H1 Associated With Nucleosome Arrangement And Gene Transcription In Early Drosophila Embryonic Development, Jian Hu, Liang Gu, Youqiong Ye, Meizhu Zheng, Zhu Xu, Jing Lin, Yanhua Du, Mengxue Tian, Lifang Luo, Beibei Wang, Xiaobai Zhang, Zhiping Weng, Cizhong Jiang 2018 Tongji University

Dynamic Placement Of The Linker Histone H1 Associated With Nucleosome Arrangement And Gene Transcription In Early Drosophila Embryonic Development, Jian Hu, Liang Gu, Youqiong Ye, Meizhu Zheng, Zhu Xu, Jing Lin, Yanhua Du, Mengxue Tian, Lifang Luo, Beibei Wang, Xiaobai Zhang, Zhiping Weng, Cizhong Jiang

Open Access Articles

The linker histone H1 is critical to maintenance of higher-order chromatin structures and to gene expression regulation. However, H1 dynamics and its functions in embryonic development remain unresolved. Here, we profiled gene expression, nucleosome positions, and H1 locations in early Drosophila embryos. The results show that H1 binding is positively correlated with the stability of beads-on-a-string nucleosome organization likely through stabilizing nucleosome positioning and maintaining nucleosome spacing. Strikingly, nucleosomes with H1 placement deviating to the left or the right relative to the dyad shift to the left or the right, respectively, during early Drosophila embryonic development. H1 occupancy on genic ...


Identifying The 5’End Of The Camta1 Genes In Zebrafish, Morgan Fronk 2018 Brigham Young University

Identifying The 5’End Of The Camta1 Genes In Zebrafish, Morgan Fronk

Undergraduate Honors Theses

Congenital heart diseases (CHDs) are a significant cause of infant death and are frequently caused by mutations in transcription factors. Camta1 (calmodulin binding transcription activator 1) is a transcription factor that has been proposed as a modulator in embryonic heart development and a possible cause of CHDs. The only other known member of its family in vertebrates is involved in activating a hypertrophy gene program in adult heart failure. Unlike camta2, camta1 is expressed in the embryonic heart during heart looping. However, few studies have been done on camta1. In zebrafish, there are two camta1 ohnologs (homologs created through a ...


Small Rnas Gained During Epididymal Transit Of Sperm Are Essential For Embryonic Development In Mice, Colin C. Conine, Fengyun Sun, Lina Song, Jaime A. Rivera-Perez, Oliver J. Rando 2018 University of Massachusetts Medical School

Small Rnas Gained During Epididymal Transit Of Sperm Are Essential For Embryonic Development In Mice, Colin C. Conine, Fengyun Sun, Lina Song, Jaime A. Rivera-Perez, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

The small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) vs. distal (cauda) epididymis, then characterized development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, and subsequently implant inefficiently and fail soon after implantation. Remarkably, microinjection ...


Profiling Of Pluripotency Factors In Individual Stem Cells And Early Embryos, Sarah J. Hainer, Ana Boskovic, Oliver J. Rando, Thomas G. Fazzio 2018 University of Massachusetts Medical School

Profiling Of Pluripotency Factors In Individual Stem Cells And Early Embryos, Sarah J. Hainer, Ana Boskovic, Oliver J. Rando, Thomas G. Fazzio

University of Massachusetts Medical School Faculty Publications

Major cell fate decisions are governed by sequence-specific transcription factors (TFs) that act in small cell populations within developing embryos. To understand how TFs regulate cell fate it is important to identify their genomic binding sites in these populations. However, current methods cannot profile TFs genome-wide at or near the single cell level. Here we adapt the CUT&RUN method to profile chromatin proteins in low cell numbers, mapping TF-DNA interactions in single cells and individual pre-implantation embryos for the first time. Using this method, we demonstrate that the pluripotency TF NANOG is significantly more dependent on the SWI/SNF ...


C. Elegans Multidrug Resistance Protein 5 (Mrp-5) Transports Vitamin B12 From The Intestine To The Gonad To Support Embryonic Development, Huimin Na, Olga Ponomarova, Gabrielle E. Giese, Albertha J. M. Walhout 2018 University of Massachusetts Medical School

C. Elegans Multidrug Resistance Protein 5 (Mrp-5) Transports Vitamin B12 From The Intestine To The Gonad To Support Embryonic Development, Huimin Na, Olga Ponomarova, Gabrielle E. Giese, Albertha J. M. Walhout

University of Massachusetts Medical School Faculty Publications

Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of her offspring. However, the mechanism for exporting vitamin B12 from the mother to her offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that injection of vitamin B12 into the gonad of ...


Small Rnas Are Trafficked From The Epididymis To Developing Mammalian Sperm, Upasna Sharma, Fengyun Sun, Brian Reichholf, Veronika Herzog, Stefan Ameres, Oliver J. Rando 2017 University of Massachusetts Medical School

Small Rnas Are Trafficked From The Epididymis To Developing Mammalian Sperm, Upasna Sharma, Fengyun Sun, Brian Reichholf, Veronika Herzog, Stefan Ameres, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

RNAs present in mature mammalian sperm are delivered to the zygote at fertilization, where they have the potential to affect early development. The biogenesis of the small RNA payload of mature sperm is therefore of great interest, as it may be a target of signaling pathways linking paternal conditions to offspring phenotype. Recent studies have suggested the surprising hypothesis that the small RNA payload carried by mature sperm may include RNAs that were not synthesized during testicular spermatogenesis, but that are instead delivered to sperm during the process of post-testicular maturation in the epididymis. To further test this hypothesis, we ...


Embryonic Transcription Factor Expression In Mice Predicts Medial Amygdala Neuronal Identity And Sex-Specific Responses To Innate Behavioral Cues., Julieta E Lischinsky, Katie Sokolowski, Li Peijun, Shigeyuki Esumi, Yasmin Kamal, Meredith Goodrich, Livio Oboti, Timothy R Hammond, Meera Krishnamoorthy, Daniel Feldman, Molly Huntsman, Judy Liu, Joshua G Corbin 2017 George Washington University

Embryonic Transcription Factor Expression In Mice Predicts Medial Amygdala Neuronal Identity And Sex-Specific Responses To Innate Behavioral Cues., Julieta E Lischinsky, Katie Sokolowski, Li Peijun, Shigeyuki Esumi, Yasmin Kamal, Meredith Goodrich, Livio Oboti, Timothy R Hammond, Meera Krishnamoorthy, Daniel Feldman, Molly Huntsman, Judy Liu, Joshua G Corbin

Pediatrics Faculty Publications

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and ...


Mechanism For Generation Of Left Isomerism In Ccdc40 Mutant Embryos, Kelsey Sugrue, Irene E. Zohn 2017 George Washington University

Mechanism For Generation Of Left Isomerism In Ccdc40 Mutant Embryos, Kelsey Sugrue, Irene E. Zohn

Pediatrics Faculty Publications

Leftward fluid flow in the mouse node is generated by cilia and is critical for initiating asymmetry of the left-right axis. Coiled-coil domain containing-40 (Ccdc40) plays an evolutionarily conserved role in the assembly of motile cilia and establishment of the left-right axis. Approximately one-third of Ccdc40lnks mutant embryos display situs defects and here we investigate the underlying mechanism. Ccdc40lnks mutants show delayed induction of markers of the left-lateral plate mesoderm (L-LPM) including Lefty1, Lefty2 and Nodal. Consistent with defective cilia motility compromising fluid flow across the node, initiation of asymmetric perinodal Cerberus like-2 (Cerl2) expression is delayed and ...


Dreadlocks (Dock) Is Necessary To Regulate Growth Of The Germline Ring Canals In The Developing Drosophila Melanogaster Egg Chamber, Olivia Crowe 2017 Butler University

Dreadlocks (Dock) Is Necessary To Regulate Growth Of The Germline Ring Canals In The Developing Drosophila Melanogaster Egg Chamber, Olivia Crowe

Undergraduate Honors Thesis Collection

Infertility is a prevalent issue in the United States, impacting 1.5 million women (1). A possible cause of infertility is defects in gametogenesis, or the formation of sperm and egg. Therefore, understanding the basic mechanisms that promote normal gamete formation could impact our understanding of infertility. The Drosophila melanogaster egg develops from an organ-like structure called an egg chamber. The egg chamber is composed of a central cluster of 16 germ cells that are connected to one another by intercellular bridges, called ring canals. These ring canals are composed of filamentous actin and allow the transfer of materials from ...


A Low-Cost Time-Lapse Imaging System Developed For Documentation Of Human Pre-Implantation Embryogenesis In Clinical Ivf Settings, Christine E. Hennigan Miss 2017 University of Colorado Boulder

A Low-Cost Time-Lapse Imaging System Developed For Documentation Of Human Pre-Implantation Embryogenesis In Clinical Ivf Settings, Christine E. Hennigan Miss

Undergraduate Honors Theses

Infertility is a disease of the reproductive system that affects many women of various ages, races, and socioeconomic factors across the world (CDC, WHO, 2017). The expensive nature of treatments for infertility, such as in vitro fertilization (IVF), has been combated with a simplified culture system (SCS) developed in the Van Blerkom lab (Van Blerkom et al., 2013). This recent advancement in clinical IVF procedures has prompted an effort to develop additional, low-cost technology able to help assess pre-implantation embryogenesis development and competence. This study examines the development and application of a low-cost, simplified, time-lapse imaging system that has shown ...


Human Oocytes And Embryos Viewed By Time-Lapse Videography, And The Development Of An Embryo Deselection Model, Yanhe Liu 2016 Edith Cowan University

Human Oocytes And Embryos Viewed By Time-Lapse Videography, And The Development Of An Embryo Deselection Model, Yanhe Liu

Theses: Doctorates and Masters

Despite its wide application today, in vitro fertilization (IVF) treatment continues to have relatively low efficacy, largely due to inaccuracy in selecting the best quality embryo(s) from the cohort for transfer. Novel methodologies for improved selection are being developed, and time-lapse observation of human embryos is gaining increasing popularity due to the more detailed morphokinetic information obtained plus uninterrupted culture conditions. The morphokinetic information enables the use of quantitative timings in developmental milestones of embryos and qualitative measures of abnormal biological events, to assist embryo selection/deselection. This project aimed to identify current limitations in the use of such ...


The Arp2/3 Complex Is Essential At Multiple Stages Of Neural Development., Fu-Sheng Chou, Pei-Shan Wang 2016 Children's Mercy Hospital

The Arp2/3 Complex Is Essential At Multiple Stages Of Neural Development., Fu-Sheng Chou, Pei-Shan Wang

Manuscripts, Articles, Book Chapters and Other Papers

During development of the nervous system, radial glial cells perform self-renewing asymmetric divisions and give rise to intermediate progenitor cells (IPC) and neurons. The neuronally committed IPC subsequently undergo multiple rounds of transient amplification and migrate outwards to form cortical layers as they continue to differentiate into mature neurons. Maturing neurons extend protrusions on their cell surface to form neurites, a process called neuritogenesis. Neurite formation results in the establishment of dendrites and axons for synapse formation, which is essential for sensory and motor functions and even higher-level functioning including memory formation and cognitive function, as well as shaping of ...


Do Induced Pluripotent Stem Cells Resolve The Ethical And Legal Issues Generated By Human Embryonic Stem Cells?, Samantha J. Henson 2015 Royal College of Surgeons in Ireland

Do Induced Pluripotent Stem Cells Resolve The Ethical And Legal Issues Generated By Human Embryonic Stem Cells?, Samantha J. Henson

Masters theses/dissertations - taught courses

The field of stem cell technology has seen an exponential growth over the last decade. Due to this, little attention has been paid as to whether this new technology adequately improves on previous research models, or indeed if it causes any ethical or legal issues itself. Of particular interest is whether Induced Pluripotent Stem Cells resolve the ethical and legal issues which have been generated by Human Embryonic Stem Cells. The ethical issues of note relate to the definition of personhood and moral status, the debate on when these can be ascribed, the consequences of utilising embryos for research, and ...


Subcellular Metabolite And Lipid Analysis Of Xenopus Laevis Eggs By Laesi Mass Spectrometry, Bindesh Shrestha, Prabhakar Sripadi, Brent R. Reschke, Holly D. Henderson, Matthew J. Powell, Sally Ann Moody, Akos Vertes 2014 George Washington University

Subcellular Metabolite And Lipid Analysis Of Xenopus Laevis Eggs By Laesi Mass Spectrometry, Bindesh Shrestha, Prabhakar Sripadi, Brent R. Reschke, Holly D. Henderson, Matthew J. Powell, Sally Ann Moody, Akos Vertes

Anatomy and Regenerative Biology Faculty Publications

Xenopus laevis eggs are used as a biological model system for studying fertilization and early embryonic development in vertebrates. Most methods used for their molecular analysis require elaborate sample preparation including separate protocols for the water soluble and lipid components. In this study, laser ablation electrospray ionization (LAESI), an ambient ionization technique, was used for direct mass spectrometric analysis of X. laevis eggs and early stage embryos up to five cleavage cycles. Single unfertilized and fertilized eggs, their animal and vegetal poles, and embryos through the 32-cell stage were analyzed. Fifty two small metabolite ions, including glutathione, GABA and amino ...


Investigating A Role For The Ccaat/Enhancer-Binding Protein Δ In The Developing Zebrafish, Alisha Jennifer Beirl 2014 Portland State University

Investigating A Role For The Ccaat/Enhancer-Binding Protein Δ In The Developing Zebrafish, Alisha Jennifer Beirl

Dissertations and Theses

The CCAAT/enhancer-binding protein delta (C/EBPδ) is a highly conserved transcription factor capable of regulating numerous cell fate processes, such as cell growth, differentiation, proliferation and apoptosis. C/EBPδ is inducible during cellular stress responses, including inflammation and responses to growth factor deprivation or thermal stress. C/EBPδ is stress-inducible in a diversity of fishes, including the zebrafish Danio rerio; however, little is known about its role in fish development. Here I show that overexpression of C/EBPδ leads to severe developmental defects, including reduced body length, edema, liver malformation and retinal abnormalities. The proportion of individuals that display ...


The Dn2 Myeloid-T (Dn2mt) Progenitor Is A Target Cell For Leukemic Transformation By The Tlx1 Oncogene, Lynnsey A. Zweier-Renn, Irene Riz, Teresa S. Hawley, Robert G. Hawley 2013 George Washington University

The Dn2 Myeloid-T (Dn2mt) Progenitor Is A Target Cell For Leukemic Transformation By The Tlx1 Oncogene, Lynnsey A. Zweier-Renn, Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Introduction: Inappropriate activation of the TLX1 (T-cell leukemia homeobox 1) gene by chromosomal translocation is a recurrent event in human T-cell Acute Lymphoblastic Leukemia (T-ALL). Ectopic expression of TLX1 in murine bone marrow progenitor cells using a conventional retroviral vector efficiently yields immortalized cell lines and induces T-ALL-like tumors in mice after long latency.

Methods: To eliminate a potential contribution of retroviral insertional mutagenesis to TLX1 immortalizing and transforming function, we incorporated the TLX1 gene into an insulated self-inactivating retroviral vector.

Results: Retrovirally transduced TLX1-expressing murine bone marrow progenitor cells had a growth/survival advantage and readily gave rise to ...


An Extra-Embryonic Wnt Signaling Event Controls Gastrulation In Mice: A Dissertation, Giovane G. Tortelote 2012 University of Massachusetts Medical School

An Extra-Embryonic Wnt Signaling Event Controls Gastrulation In Mice: A Dissertation, Giovane G. Tortelote

GSBS Dissertations and Theses

The formation of the anterior-posterior axis requires a symmetry-breaking event that starts gastrulation. Ultimately, the morphogenetic movements of gastrulation reshape the embryo to its final tri-dimensional form. In mouse embryos, the identity of the molecule that breaks the bilateral symmetry and sets in motion gastrulation remains elusive. The Wnt signaling pathway plays a pivotal role during axial specification and gastrulation in metazoans. Loss-of-function experiments have demonstrated a requirement of Wnt3 for gastrulation in mice. But because Wnt3 is expressed sequentially in two tissues, the visceral endoderm and the epiblast, its tissue specific requirements remain uncertain. Here, we report that embryos ...


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