Cerebral Organoids Derived From Sandhoff Disease-Induced Pluripotent Stem Cells Exhibit Impaired Neurodifferentiation, 2018 National Institutes of Health
Cerebral Organoids Derived From Sandhoff Disease-Induced Pluripotent Stem Cells Exhibit Impaired Neurodifferentiation, Maria L. Allende, Emily K. Cook, Bridget C. Larman, Adrienne Nugent, Jacqueline M. Brady, Diane Golebiowski, Miguel Sena-Esteves, Cynthia J. Tifft, Richard L. Proia
Open Access Articles
Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease ...
A Cre-Inducible Dux4 Transgenic Mouse Model For Investigating Facioscapulohumeral Muscular Dystrophy, 2018 University of Massachusetts Medical School
A Cre-Inducible Dux4 Transgenic Mouse Model For Investigating Facioscapulohumeral Muscular Dystrophy, Takako I. Jones, Peter L. Jones
Open Access Articles
The Double homeobox 4 (DUX4) gene is an important regulator of early human development and its aberrant expression is causal for facioscapulohumeral muscular dystrophy (FSHD). The DUX4-full length (DUX4-fl) mRNA splice isoform encodes a transcriptional activator; however, DUX4 and its unique DNA binding preferences are specific to old-world primates. Regardless, the somatic cytotoxicity caused by DUX4 expression is conserved when expressed in cells and animals ranging from fly to mouse. Thus, viable animal models based on DUX4-fl expression have been difficult to generate due in large part to overt developmental toxicity of low DUX4-fl expression from leaky transgenes. We have ...
Transient Transcriptional Silencing Alters The Cell Cycle To Promote Germline Stem Cell Differentiation In Drosophila, 2018 University at Albany, State University of New York
Transient Transcriptional Silencing Alters The Cell Cycle To Promote Germline Stem Cell Differentiation In Drosophila, Pooja Flora, Sean Schowalter, Siuwah Wong-Deyrup, Matthew Degennaro, Mohamad Ali Nasrallah, Prashanth Rangan
Open Access Articles
Transcriptional silencing is a conserved process used by embryonic germ cells to repress somatic fate and maintain totipotency and immortality. In Drosophila, this transcriptional silencing is mediated by polar granule component (pgc). Here, we show that in the adult ovary, pgc is required for timely germline stem cell (GSC) differentiation. Pgc is expressed transiently in the immediate GSC daughter (pre-cystoblast), where it mediates a pulse of transcriptional silencing. This transcriptional silencing mediated by pgc indirectly promotes the accumulation of Cyclin B (CycB) and cell cycle progression into late-G2 phase, when the differentiation factor bag of marbles (bam) is expressed. Pgc ...
Cloning And Spatiotemporal Expression Of Xenopus Laevis Apolipoprotein Ci, 2018 Thermo Fisher Scientific
Cloning And Spatiotemporal Expression Of Xenopus Laevis Apolipoprotein Ci, Jyotsna Sridharan, Tomomi Haremaki, Daniel C. Weinstein
Publications and Research
Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI has been implicated in atherosclerosis and Alzheimer’s disease in humans. In this study we report the isolation of Xenopus laevis apoCI and describe the expression pattern of this gene during early development, using reverse transcription polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is enriched in the dorsal ectoderm during gastrulation, and is subsequently expressed in sensory placodes, neural tube and cranial neural crest. These data suggest as yet uncharacterized roles for ApoCI during early ...
Jak/Stat Signaling Regulates Gametogenesis And Age-Related Reproductive Maintenance, 2018 University of Kentucky
Jak/Stat Signaling Regulates Gametogenesis And Age-Related Reproductive Maintenance, Michelle Suzanne Giedt
Theses and Dissertations--Biology
Cell signaling is central to integration of internal and external cues that regulate development and homeostasis. Most development is thought of as pre-adult, but limited developmental processes occur in adults. Gametogenesis incorporates elements of both these facets, with a distinct developmental plan for gamete synthesis which is regulated by integration of homeostatic inputs such as nutrient status, and environmental cues. Signaling pathways integrate and transduce information from these cues to evoke a response. A decline in homeostasis and subsequent cues occurs over time, in the case of reproductive tissues leading to a progressive loss of fertility. The Janus Kinase and ...
Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, 2018 CUNY City College
Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack
Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating ...
Rlim-Dependent And -Independent Pathways For X Chromosome Inactivation In Female Escs, 2017 University of Massachusetts Medical School
Rlim-Dependent And -Independent Pathways For X Chromosome Inactivation In Female Escs, Feng Wang, Kurtis N. Mccannell, Ana Boskovic, Xiaochun Zhu, Jongdae Shin, Jun Yu, Judith Gallant, Meg Byron, Jeanne B. Lawrence, Lihua Julie Zhu, Stephen N. Jones, Oliver J. Rando, Thomas G. Fazzio, Ingolf Bach
University of Massachusetts Medical School Faculty Publications
During female mouse embryogenesis, two forms of X chromosome inactivation (XCI) ensure dosage compensation from sex chromosomes. Beginning at the four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X (Xp), and this pattern is maintained in extraembryonic cell types. Epiblast cells, which give rise to the embryo proper, reactivate the Xp (XCR) and undergo a random form of XCI (rXCI) around implantation. Both iXCI and rXCI depend on the long non-coding RNA Xist. The ubiquitin ligase RLIM is required for iXCI in vivo and occupies a central role in current models of rXCI. Here, we demonstrate the existence of ...
Identifying Genetic Factors Influencing Sperm Mobility Phenotype In Chicken Using Genome Wide Association Studies, Primordial Germ Cell Transplantation, And Rnaseq., 2017 University of Arkansas, Fayetteville
Identifying Genetic Factors Influencing Sperm Mobility Phenotype In Chicken Using Genome Wide Association Studies, Primordial Germ Cell Transplantation, And Rnaseq., Sohita Ojha
Theses and Dissertations
Sperm mobility is a major determinant of male fertility in chicken. In spite of low heritability of reproductive traits, sperm mobility has high heritability index which suggests presence of quantitative trait loci (QTLs) governing the trait. Our research focused on three objectives: i) to identify the QTLs affecting low mobility phenotype in chicken, ii) to understand the impact of Sertoli-cells and germ cells interactions in influencing the mobility phenotype and iii) to identify the genes and gene networks differentially expressed in male and female PGCs. To detect the QTLs, genome wide association studies (GWAS) was conducted which revealed the presence ...
Temporal Regulation Of Chromatin During Myoblast Differentiation, 2017 Kyushu University, Japan
Temporal Regulation Of Chromatin During Myoblast Differentiation, Akihito Harada, Yasuyuki Ohkawa, Anthony N. Imbalzano
UMass Metabolic Network Publications
The commitment to and execution of differentiation programmes involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The ...
Butyl Benzyl Phthalate (Bbp) Induces Caudal Defects During Embryonic Development, 2017 Sacred Heart University
Butyl Benzyl Phthalate (Bbp) Induces Caudal Defects During Embryonic Development, Nicole Roy, Ewelina Zambrzycka, Jenna Santangelo
Biology Faculty Publications
Butyl benzyl phthalate (BBP) is commonly added during the manufacturing of plastics to increase flexibility and elasticity. However, BBP leaches off of plastic and environment presence has been detected in soil, groundwater and sediment potentially effecting organisms in the environment. Given the widespread uses of BBP in household, consumer goods and the presence of BBP in the environment, studies on developmental toxicity are needed. Here, we use a zebrafish model to investigate the early developmental toxicity of BBP. We treated gastrula staged embryos with increasing concentrations of BBP and noted concentration-dependent defects in caudal tail development, but the effect was ...
Intraflagellar Transporter Protein (Ift27), An Ift25 Binding Partner, Is Essential For Male Fertility And Spermiogenesis In Mice, Yong Zhang, Hong Liu, Wei Li, Zhengang Zhang, Xuejun Shang, David Zhang, Yuhong Li, Shiyang Zhang, Junpin Liu, Rex A. Hess, Gregory J. Pazour, Zhibing Zhang
Open Access Articles
Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were ...
Within-Litter Birth Weight Variation In The Domestic Pig And Its Relation To Pre-Weaning Survival, Weight Gain, And Variation In Weaning Weights, Barry N. Milligan, David Fraser, Donald L. Kramer
David Fraser, Ph.D.
To determine the relationship between within-litter birth weight variation and pre-weaning survival and weight gain, and to provide practical guidance on fostering low-birth-weight piglets, we analyzed piglet survival and weight gain in litters of piglets from 52 sows followed through eight consecutive parities. Litters with high variation in birth weight had more deaths, especially if the litter’s mean birth weight was low. High variation in birth weight was also associated with high variation in weaning weight, but was not significantly related to mean weaning weight. Piglets with birth weights well below the range of most of the litter (‘low-birth-weight ...
The Effect Of Littermate Weight On Survival, Weight Gain, And Suckling Behavior Of Low-Birth-Weight Piglets In Cross-Fostered Litters, Barry N. Milligan, David Fraser, Donald L. Kramer
David Fraser, Ph.D.
Objective: To determine whether low-birth-weight piglets show better survival, weight gain, and suckling behavior when grouped with other small piglets by cross-fostering. Methods: We manipulated the number and size of foster littermates for low-birth-weight piglets in 31 small (eight or nine piglets) and 22 large (11 or 12 piglets) litters. Experimental litters were composed of four to six piglets of lowest birth weight and either four to six slightly heavier or four to six much heavier piglets from two combined litters. Results: Low-birth-weight piglets raised with much heavier littermates had somewhat lower survival rates, but showed no tendency towards lower ...
Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, 2017 Murray State University
Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley N. Munie
Steeplechase: An ORCA Student Journal
Autophagy, the cell's recycling system, is a highly-conserved survival mechanism of the cell. Autophagy has been implicated in the mediation of the removal of cytotoxic aggregates, such as those linked to neurodegenerative disorders like Huntington and Alzheimer disease. Studies in several model organisms have identified numerous genes involved in mediating autophagy, including the Puromycin sensitive aminopeptidase (Psa). The Caenorhabditis elegans orthologue of Psa, pam-1, also governs fertility. Along with apoptosis, a form of regulated cell death, autophagy has been found to be required for efficient C. elegans oogenesis. When autophagy is suppressed through RNAi in worms harboring a pam-1 ...
The Hoxd Cluster Is A Dynamic And Resilient Tad Boundary Controlling The Segregation Of Antagonistic Regulatory Landscapes, Eddie Rodriguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre J. Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hanh Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule
Program in Systems Biology Publications and Presentations
The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos, we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region ...
An Undergraduate Laboratory Manual For Analyzing A Crispr Mutant With A Predicted Role In Regeneration, Susan Walsh, Ashley Becker, Paxton S. Sickler, Damian G. Clarke, Erin Jimenez
Exposing students to undergraduate research has reportedly improved students’ development of knowledge and skills in the laboratory, self-efficacy, satisfaction with their research, retention, and perseverance when faced with obstacles. Furthermore, utilizing authentic course-based undergraduate research experiences (CUREs) includes all students enrolled in the class, giving those who may not otherwise have access to an independent undergraduate research project an opportunity to engage in the scientific process in context of an original, unanswered question. In the fall of 2016, second semester introductory biology students conducted a semester-long research project on the transcription factor Lin28a to determine the effect of Lin28a on ...
Materials And Method For Modifying A Biochemical Component In A Plant, 2017 Iowa State University
Materials And Method For Modifying A Biochemical Component In A Plant, Ling Li, Eve Syrkin Wurtele
A method of modifying the amount of at least one biochemical component in a plant comprising expressing Qua-Quine Starch (QQS) in the plant, the wild-type of which does not express QQS; a transgenic plant, or part thereof, which comprises and expresses QQS as a transgene and in which the amount of at least one biochemical component is modified; a tissue culture of regenerable cells of the transgenic plant; a vector comprising a nucleotide sequence, which encodes the coding sequence of QQS, operably linked to a non-native promoter, which promotes expression of the nucleotide sequence in a plant, which is other ...
Jennifer Maurer Phd Thesis.Pdf, 2017 University of Massachusetts Medical School
Jennifer Maurer Phd Thesis.Pdf, Jennifer Maurer
Xist Rna: A Window Into The Broader Role Of Rna In Nuclear Chromosome Architecture, 2017 University of Massachusetts Medical School
Xist Rna: A Window Into The Broader Role Of Rna In Nuclear Chromosome Architecture, Kevin Creamer, Jeanne B. Lawrence
Open Access Articles
XIST RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how XIST RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of XIST into a trisomic autosome demonstrates remarkable capacity of XIST RNA to localize and comprehensively silence that autosome. Thus, XIST does not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggested XIST localization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment ...
Optimizing Sperm Collection Procedures In Zebrafish, 2017 University of South Carolina Aiken
Optimizing Sperm Collection Procedures In Zebrafish, Madelyn B. Wasden, Rachel L. Roberts, April Delaurier
Journal of the South Carolina Academy of Science
Zebrafish are a highly-valued model organism used for developmental biology research. Zebrafish can be used for genetic manipulation and hence, many mutant and transgenic lines exist. It is impractical to maintain lines of adult zebrafish, due to resource constraints and the need to continuously produce new generations. Therefore, a practical way to preserve zebrafish lines is to freeze sperm and retrieve lines using in vitro fertilization of fresh eggs. Most existing in vitro protocols used by research labs have a wide variety of fertilization rates (ranging from 0% to >90%). Due to this variability, lines may be at risk of ...