Cell and Developmental Biology Commons^™

The Effects Of Vitamin K On Neuronal Ferroptosis, Chelsey P. Eighmey

Electronic Theses & Dissertations (2024 - present)

Dementia is a crippling illness affecting millions worldwide causing significant public health burdens with long-term care. The lack of treatment options results in many years of suffering for affected individuals and their loved ones who often become primary caretakers. Decades of study have focused on treating dementia with little-to-no success, so an emphasis is needed on attempting to prevent disease progression altogether. This research explored vitamin K as a potential strategy for prevention of dementia onset or progression through the mechanism of suppressing ferroptosis. Ferroptosis is a type of cell death suggested to contribute to the hallmark traits of Alzheimer’s …

Stem Cell-Derived Developmental Models For Translational Evaluation Of Disease And Therapy, Maria B. Paredes-Espinosa

Electronic Theses & Dissertations (2024 - present)

Human development as well as congenital and adult diseases emerge from coordinated interactions among multiple cell types, regulatory programs, and tissue compartments that remain largely unresolved. Conventional simple lineage-restricted in vitro systems poorly capture this complexity. My dissertation uses human stem cell-derived developmental models to study human cardiac morphogenesis and heart diseases and application of a networked neuron platform to explore senescence-associated neurodegeneration impact on Alzheimer’s neurons.

Elongating multi-lineage organized cardiac (EMLOC) gastruloids are a synthetic embryology model that co-generates contractile cardiomyocyte populations alongside mesenchymal, endothelial, epicardial-like, neural crest-associated, and neuronal cells within a shared in vitro developmental environment. Single-cell …

Multifunctional And Adaptive: Tracking How Fibroblasts Respond To Tissue Injury And Facilitate Tissue Remodeling, Joey R. Tavarez

Electronic Theses & Dissertations (2024 - present)

Fibrosis is characterized by an accumulation of proteins in the extracellular matrix (ECM) that results in altered tissue architecture and reduced organ function. In the salivary glands, fibrosis leads to loss of saliva, dysbiosis of the oral microbiome, an increase in oral infections, difficulty in digestion of food and an overall reduction in the quality of life. Understanding the progression of fibrosis and how it affects human health is a crucial step for designing effective therapeutics. Understanding fibroblast function is integral to advancing the field due to the many roles they play in maintaining the ECM. To perform preliminary analysis, …

The Role Of The Nasal Migratory Mass In Olfactory Bulb Formation And Fertility, Charisse Martin

Electronic Theses & Dissertations (2024 - present)

The olfactory migratory mass plays an essential role in the development of the olfactory bulb by facilitating the migration of the gonadotropin-releasing hormone neurons from the olfactory placode to the pre-optic hypothalamic area in the brain. In mammals, the migration of GnRH neurons is critical for establishing the hypothalamic-pituitary-gonadal axis (HPG axis), which regulates reproductive function through the production and secretion of gonadotropins. Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) instruct the gonads to function appropriately, ensuring sexual maturation and fertility. Disruptions in this migratory pathway have been linked with Kallmann syndrome, a condition characterized by low levels of GnRH, …

Elucidating The Effects Of Environmental And Physiological Conditions On Stem Cell Regulation In Vivo, Nimmy John

Electronic Theses & Dissertations (2024 - present)

The Notch signaling pathway is a highly conserved intercellular signaling pathway that any dysregulation can lead to a variety of human diseases. These diseases are further exacerbated by various environmental, pathological and genetic conditions. Previous studies have shown that these conditions have been known to affect the Notch transcriptional response. However, the molecular mechanisms by which such conditions influence Notch signaling remained largely unknown. Moreover, most Notch studies have relied on in vitro systems and indirect reporters, which can miss the dynamic and contextual nature of Notch signaling. Here, we systematically analyzed the effects of these conditions with single molecule …

Transcriptome-Wide Gene Expression Analysis Of Skeletal Muscles Of Duchenne Muscular Dystrophy Mouse Models And Patients, Olivia N. Ransiear

Electronic Theses & Dissertations (2024 - present)

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive muscle degenerative disease that frequently proves fatal by age 30. It primarily affects adolescent males with symptoms appearing as early as age 6. Patients quickly lose their ability to walk due to muscle weakness and are confined to wheelchairs for the remainder of their lives. DMD is caused by a mutation in the dystrophin gene. Without dystrophin, mechanical stress, injury, or shock takes a drastic toll on muscle tissue and muscle stem cells, rendering them unable to regenerate or be repaired. This results in a rapid loss of muscular strength and muscle …

Unveiling The Cell Composition Of The Olfactory Migratory Mass: Perspectives On Terminal Nerve Formation, Olfactory Development, And Migration Of The Gnrh-1 Neurons, Enrico Amato Jr.

Electronic Theses & Dissertations (2024 - present)

Puberty is a postnatal developmental process required to initiate key sexual maturation events that are necessary for the propagation of species. Signals to initiate these events first begin with the Gonadotropin releasing hormone-1 (GnRH-1) neurons within the hypothalamus. The hormone GnRH-1 released by these neurons is crucial for puberty, fertility and reproductive processes by establishing the hypothalamic-pituitary-gonadal (HPG) axis, regulating release of sex hormones (Progesterone, Estrogen, Testosterone). Conditions related to inability of the GnRH-1 neurons to correctly release GnRH-1 can lead to aberrant or delayed puberty, a condition known as hypogonadotropic hypogonadism (HH). Interestingly, some patients with the hormonal disorder …

Contactin2(Cntn2)Creert2 Mouse Line, A New Genetic Tool For Temporal Control To Trace The Developing Neurons In The Nose, Alexis M. Semon

Electronic Theses & Dissertations (2024 - present)

Neuronal migration is a vital process in embryonic development. In rodents, the very first neurons that originate from the olfactory placode migrate toward the developing brain as part of the migratory mass. This migratory mass includes Gonadotropin-releasing hormone-1 (GnRH-1) neurons, pioneer/terminal nerve (TN) neurons, and olfactory ensheathing cells—a type of glial cell.

Contactin-2 (Cntn2), also referred to as transiently expressed axonal surface glycoprotein-1 (TAG-1), belongs to the contactin family of proteins, which is part of the immunoglobulin superfamily of cell adhesion molecules. Cntn2 has been extensively utilized as a transient/stage-specific molecular marker for various neuronal populations, including commissural neurons of …

Role Of M6a Rna Methylation In Skeletal Muscle Regeneration, Isreal Ayobami Onifade

Legacy Theses & Dissertations (2009 - 2024)

Skeletal muscle is essential in orchestrating voluntary movement and contributes to approximately half of the body's overall mass. Dysregulation in proper skeletal muscle development can lead to muscle degenerative disorders, such as severe Duchenne Muscular Dystrophy (DMD). Understanding the process of muscle development has been the central focus of numerous biological studies, focusing on myogenic transcription factors and signaling molecules like Pax3, Pax7, Myf5, MyoD, WNT, TGF-β, and BMP, IGF1, AKT/mTOR pathway. Also, studies have suggested that m6A (N6-methyladenosine) plays a crucial role in various biological processes, including skeletal muscle regeneration and development. m6A modification is the prevalent form of …

The Effects Of The Clinically Relevant Synthetic Progestin, 17-Α-Hydroxyprogesterone Caproate, On Neural Development And Behavior., Paige L. Graney

Legacy Theses & Dissertations (2009 - 2024)

The synthetic progestin, 17-α -hydroxyprogesterone caproate (17-OHPC) has beencommonly prescribed during gestation to reduce preterm delivery in individuals at risk (Meis et al., 2003). In singleton pregnancies, 17-OHPC treatment begins during the second trimester, around gestational weeks 16-20, and continues until the end of the third trimester, around week 37 (Berghella, 2012). Although the fetus is not directly administered 17-OHPC, previous research demonstrated that 17-OHPC was transferred from the maternal unit to the fetal unit of the placenta in situ, was detectable in maternal and fetal blood up to 44 days following the last injection (Caritis et al., 2012; Hemauer …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Transcription And Translation Regulation Of Germ Cell To Maternal Transition, Noor Kotb

Electronic Theses & Dissertations (2024 - present)

In sexually reproducing organisms, the process of gametogenesis produces mature eggs and sperms required for fertilization to occur. The egg's quality is crucial for the healthy development of the next generation, making oogenesis a tightly regulated process with multiple benchmarks. To investigate the intricacies of oogenesis, we utilized the Drosophila oogenesis system as our primary model. This choice was motivated by several factors. Firstly, the process of egg development in Drosophila is conserved across species, making it a valuable proxy for understanding oogenesis in other organisms, including humans. Secondly, Drosophila melanogaster has long been established as a powerhouse in genetic …

Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery

Legacy Theses & Dissertations (2009 - 2024)

Sjögren’s syndrome is an autoimmune condition characterized by a dysfunction in the lachrymal and salivary glands which results in dry eyes and dry mouth. Since its first description in 1892, the disease is one of the most common autoimmune diseases after lupus erythematosus and rheumatoid arthritis in the United States. Despite its high prevalence in the general population, Sjögren’s syndrome remains hard to diagnose due to the wide range of symptoms associated with the disease that is also shared by other conditions. Furthermore, the mechanisms behind the pathogenesis are not properly understood even though multiple factors have been proposed to …

N6-Methyladenosine Rna Modifications In Myogenesis / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Marina Danielle Infantado

Legacy Theses & Dissertations (2009 - 2024)

Myogenesis involves skeletal muscle stem cells (MuSCs) that produce and regenerate skeletal muscle during regular growth and repair. However, when this system fails to function normally, it can lead to musculoskeletal diseases like Duchenne Muscular Dystrophy (DMD). Therefore, it is important to study the molecular mechanisms behind this developmental process in order to seek therapies and solutions for these types of diseases. Our interest lies in the field of epitranscriptomics, which focuses on post-transcriptional ribonucleic acid (RNA) modifications, particularly N6-methyladenosine (m6A), which involves the addition of a methyl group to the adenosine nucleotide, a process that is mediated by the …

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …

Translation Control Tunes Drosophila Oogenesis, Elliot T. Martin

Legacy Theses & Dissertations (2009 - 2024)

The decision of a stem cell to either self-renew or differentiate is controlled by specific cellularpathways that can act at the level of transcription, translation, or post-translation. To study the regulation of these pathways in-vivo, I have used the female Drosophila germline as a model system. Each of the steps from germline stem cell (GSC) to egg require changes in cellular pathways. These changes can occur at the level of transcription, post-transciption, translation, or post-translation . Decades of research has elucidated many of the changes to gene that occur during oogenesis, however, many players in this process still remain mysterious. …

Role Of H3k4 Methylation In Myogenesis, Regeneration, And Muscle Disease / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Hannah Emily Shippas

Legacy Theses & Dissertations (2009 - 2024)

Muscles are a crucial part of an organism’s wellbeing, as defects in distinct types of muscles can be lethal. Our voluntary muscles, skeletal muscles, go through distinct regeneration phases before reaching maturity. With its own pool of stem cells, muscles have a large potential for regeneration. This potential has led scientists into looking closely at the steps that lead a muscle stem cell into muscle fiber, also known as myogenesis. As a muscle cell moves through myogenesis, genes are led to be turned on/off with different epigenetic mechanisms, one being histone modifications. A methylation modification on the 4th Lysine on …

Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa

Legacy Theses & Dissertations (2009 - 2024)

Organogenesis is the process organs go through where cellular communications coordinate all a developing organ needs. What organs need are more cells, in the right place, doing the right job. In the salivary gland, we know that stromal cells are important for organogenesis and that they coordinate the epithelium’s form and functions. However, specific stromal contributions have focused on epithelial quantity and placement. There is less information about how the stroma directs the epithelium towards certain functions. Here we used organoids as a model for understanding what stromal signaling directs epithelial cell fate. We found that stromal cell state is …

Mechanisms Underlying Pre- And Postnatal Development Of The Mouse Vomeronasal Organ, Raghu Ram Katreddi

Legacy Theses & Dissertations (2009 - 2024)

The Vomeronasal organ (VNO) is a specialized olfactory sensory organ located in the ventral region of the nasal cavity in rodents. The vomeronasal epithelium (VNE) of rodents is composed of 2 major types of vomeronasal sensory neurons (VSNs): 1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gi2, and 2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Go. Besides these two neuronal types, VNE also accommodate a third non-neuronal cell type called Sustentacular cells that lie anatomically above apical …

Genetic Regulation Within Cellular Stress Response Pathways, Jhos M. Dufflart

Legacy Theses & Dissertations (2009 - 2024)

Cellular stress is something that a cell deals with on a regular basis. Fortunately, there are several different mechanisms that are set in place in order to deal with them. Depending on the stress present in the cell there will be different stress response pathways that are activated in order to mitigate the stress or initiate cellular death mechanisms. Transcription factors (TFs) are key components within these pathways, and this will be the focus of this thesis. TFs within mammalian stress response pathways are tasked with the essential regulation of multiple genes within these pathways and are oftentimes linked with …

Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian

Legacy Theses & Dissertations (2009 - 2024)

Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …

Rna Modification Landscape And Its Contribution To Egg Production, Ian Thomas Rapisarda

Legacy Theses & Dissertations (2009 - 2024)

Germline stem cells differentiate into mature egg or sperm cells that go through the process of fertilization which gives rise to all sexually reproducing organisms. During this process of differentiation, germ cells undergo a switch from mitosis to meiosis that allows for proper development and specification of the future gamete. The mechanisms that facilitate this shift from mitosis to meiosis, however, are not well understood. To gain insight into this process, we used Drosophila oogenesis as our model. To identify what RNA modifications are present during oogenesis we genetically enriched for each stage of development and performed mass spectrometry. We …

Study Of Primary Cilium Structure And Intraflagellar Transport, Shufeng Sun

Legacy Theses & Dissertations (2009 - 2024)

Primary cilia are hair-like protrusions that stem from the basal bodies in the cytoplasm and extend into the extracellular space to sense signals. Intraflagellar transport (IFT) functions to transport cargo molecules into and out of the ciliary compartment to assemble, maintain, and disassemble the cilia. Accurate knowledge of the three-dimensional (3D) structure of primary cilia and precise details of the IFT profile is the foundation for understanding the sensory functions of primary cilia. This work covers three aspects of primary cilia. Firstly, we obtained and analyzed the overall 3D architecture of the complete primary cilia axoneme region using serial section …

Tgfbeta1 And Stat3 As Regulators Of The Ha Synthesis And Signaling Pathway, Brenda Goretty Trevizo

Legacy Theses & Dissertations (2009 - 2024)

The studies described here explored the role of Transforming Growth Factor Beta-1 (TGFβ1) and Signal Transducer and Activator of Transcription 3 (STAT3) as potential regulators of the Hyaluronic Acid (HA) synthesis and signaling pathway in human mammary cells. Our results support previous findings in which TGFβ1, a well characterized driver of the epithelial-mesenchymal transition (EMT) has been shown to regulate HA synthesis and signaling. Interrogation of The Cancer Genome Atlas (TCGA) indicated HAS2 expression positively correlated with TGFβ1 mRNA expression in breast cancer patients and in breast cancer cell lines. RT-qPCR experiments were used to measure the expression of the …

Sensing Ribonuclease H Activity With Dna Nanoswitches, Ruju Trivedi

Biological Sciences

Ribonuclease H (RNase H) is a damage-repair protein and ribonuclease that specifically catalyzes the hydrolysis of RNA in an RNA/DNA duplex and breaks down RNA/DNA junctions. It plays an important role in a variety of biological processes including DNA replication, DNA repair, and transcription. It is also pivotal in anti-HIV drug development and the analysis of cellular processes and has been shown to be a potential therapeutic target for various neoplastic diseases. This thesis discusses a unique assay based on DNA nanoswitches to detect RNase H levels and activity. The assay is based on conformational changes of DNA nanoswitches in …

Glutamine Antagonist 6-Diazo-5-Oxo-L-Norleucine, A Hyaluronan Synthesis Inhibitor, Slows Triple Negative Breast Cancer Growth, Le Gia Cat Pham

Biological Sciences

Triple-negative breast cancers (TNBC) are the most aggressive subtype of breast cancer with few treatment options and poor outcomes. TNBCs are characterized by elevations in hexosamine biosynthetic pathway (HBP) enzyme expression, hyaluronan synthase 2 (HAS2) expression and hyaluronan (HA) production. Glutamine is an important substrate for HA production via the HBP. 6-diazo-5-oxo-L-norleucine (DON) is a well-known glutamine antagonist with validated antitumoral efficacy. This project examined the effects of DON on HA production and energy metabolism in TNBC cells. We examined the effect of DON treatment on Hs578T cells, which represent the mesenchymal stem-like subtype of TNBC. We specifically analyzed the …

The Stromal Response In Salivary Gland Injury, Kevin O'Keefe

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Tfap2e/Ap-2e Is A Transcriptional Regulator Controlling Neuronal Identity And Circuitry Formation In The Mouse Accessory Olfactory System, Jennifer M. Lin

Legacy Theses & Dissertations (2009 - 2024)

Developmental progression is driven by specific spatiotemporal gene expression, which give rise to consistently patterned organisms despite environmental and genetic variation. The specific activation of robust gene regulatory networks that define tissue structure and individual cellular identity are necessary for tissue and cell specific programs to be activated. Cellular specification is guided by the interplay of intrinsic and extrinsic signals at specific developmental timepoints. The molecular mechanisms underlying the acquisition and maintenance of individual cellular identity remains a fundamental question across biological systems. Understanding the regulatory networks controlling the acquisition of neuronal identity, diversity, and connectivity in the formation of …

Launching The Next Generation : Transcriptional Regulation During Oogenesis, Alicia K. Mccarthy

Legacy Theses & Dissertations (2009 - 2024)

Germ cells give rise to gametes and link generations by passing genetic information from parent to offspring. Gametes arise from, in many sexually reproducing organisms, germline stem cells (GSCs) which are set aside early during development. GSCs have an amazing capacity to undergo self-renewal to give rise to a pool of undifferentiated cells, while also differentiating to generate specialized germ cells such as haploid gametes. Upon female GSC differentiation, mitotically dividing germ cells can initiate meiosis, and mature within a follicle. During maturation, the specified oocyte is provided with a trust fund of RNAs and proteins for the next generation …

Role Of Smad4 Dependent Signaling In Controlling The Functioning And Connectivity Of Basal Vomeronasal Sensory Neurons, Ankana S. Naik

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT