Developmental Biology Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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

The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer

Legacy Theses & Dissertations (2009 - 2024)

Skeletal muscle plays a crucial role in coordinating voluntary movement and accounts for nearly 50% of total body mass. Dysregulation in skeletal muscle development is known to cause muscle degenerative diseases including the devastating Duchenne Muscular Dystrophy (DMD). The majority of the biological studies investigating muscle development were based on myogenic transcription factors and signaling molecules including: Pax7, Myf5, MyoD, WNT, TGF-β and BMP. After the discovery of non-coding RNAs including microRNAs, it was postulated that these molecules could regulate gene expression and thus affect differentiation and development. MicroRNAs are small non-coding RNAs (~17-25 nucleotides) that regulate gene expression negatively …

Of Donuts And Promo : In Silico Approaches To Identification Of Transcriptional Regulators Of Salivary Acinar Differentiation, Connor Cillian Duffy

Legacy Theses & Dissertations (2009 - 2024)

The salivary gland is an organ often taken for granted by most people. However, its proper function is essential for several everyday activities, such as speaking, swallowing, and tasting. As such, impaired salivary gland function, such as that caused by Sjögren’s Syndrome or radiotherapy for head and neck cancers, can lead to a significantly reduced quality of life. The cells that produce saliva in salivary glands are known as acinar cells, which arise from proacinar cells generated during embryonic development. As such, in studying the promoter regions of proacinar and acinar genes, it may be possible to identify common transcription …

Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli

Legacy Theses & Dissertations (2009 - 2024)

The contextual fear circuit, centered on the basolateral nucleus of the amygdala (BLA), is comprised of projections from the hippocampal formation and prefrontal cortex, and mediates an animals ability to learn and predict associations between the environment and biologically relevant stimuli. While the function and structure of this circuit has been well characterized in adult species, relatively little is known about its development as an animal transitions from infancy to adulthood. Recent evidence has begun to suggest that infants, juveniles, and adolescents may show remarkable heterogeneity in the behavioral, activational, and structural properties of the circuit. In this thesis, I …

Regulated Transcriptional Silencing Promotes Germline Stem Cell Differentiation In Drosophila Melanogaster, Pooja Flora

Legacy Theses & Dissertations (2009 - 2024)

Germ cells are the only cell in an organism that have the capacity to give rise to a new organism and are passed from one generation to the next. Therefore, to maintain this unique ability of totipotency and immortality, germ cells execute specific functions, such as, repression of a somatic program and contour a germ line-specific pre- and post-transcriptional gene regulatory landscape. In many sexually reproducing organisms, germ cells are formed during the earliest stages of embryogenesis and undergoes several stages of development to eventually get encapsulated by the somatic cells of the gonad. Once, in the gonad, the germ …

Chromatin-Signaling Axis Orchestrates The Formation Of Germline Stem Cell Differentiation Niche In Drosophila, Maitreyi Upadhyay

Legacy Theses & Dissertations (2009 - 2024)

Stem cells have the unique capability of self-renewing into stem cells and differentiating into several terminal cell types. Loss of either of these processes can lead to aging, progression towards degenerative diseases and cancers. Insight into how self-renewal and differentiation are regulated will have tremendous therapeutic impact. Drosophila is an excellent model system for stem cell study due to the availability of various mutants, markers and RNAi technology. In order to study stem cell biology, we use female Drosophila gonads, whose stem cell population – the germline stem cells (GSCs) gives rise to gametes.

Retinoic Acid Receptor Isoform-Specific Control Of Mouse Salivary Gland Development And Regeneration, Kara Desantis

Legacy Theses & Dissertations (2009 - 2024)

Controlled expansion and differentiation of progenitor cell populations is essential for organogenesis followed by continued maintenance of the population into and through adulthood. As the K5+ basal cell population is regulated by retinoic acid signaling, we interrogated the contribution of specific RAR isoforms to the regulation of these cells during submandibular salivary gland (SMG) organogenesis and regeneration. Retinoic acid has previously been shown to be involved in the development of the salivary gland, and recently, lack of retinoid signaling has been shown to impact the K5+ population of basal progenitor cells. Since retinoic acid is known to exert stimulatory effects …

Investigation Into The Function Of Endothelial Cells And Their Signaling In Early Salivary Gland Development, Hae Ryong Kwon

Legacy Theses & Dissertations (2009 - 2024)

Functional vasculature regulates organ formation and regeneration. Perfusion-independent and nutrition-independent endothelial regulation of epithelial patterning is of considerable interest for application in restoring parenchymal function. During murine submandibular salivary gland development, the vasculature co-develops with the epithelium; however, it is still unknown if the vasculature has instructive effects on the epithelium. A systems biological study revealed that endothelial genes are enriched in epithelial clefts, suggesting a potential involvement of endothelial cells in early morphogenesis. Using immunodepletion of the endothelial cells from the mesenchyme of reconstituted glands, a requirement for endothelial cells in epithelial patterning was demonstrated. Specifically, lobule formation was …

Myoepithelial Cell Morphogenesis And Differentiation In The Mouse Submandibular Salivary Gland In Development And Disease, Elise Marie Gervais

Legacy Theses & Dissertations (2009 - 2024)

Organogenesis is the process by which tissues organize, gain considerable size, and undergo cellular differentiation or specialization to form fully functional organs. To study the processes involved in organogenesis of branched organs, the mouse submandibular salivary gland is frequently used as a model system, as it can undergo morphogenesis and differentiation and be genetically manipulated ex vivo. The mouse submandibular salivary gland undergoes a specific process of outgrowth and invagination known as branching morphogenesis which allows for the significant increase in gland size and complexity, as well as maximization of surface area for secretion of saliva. Surrounding the mouse submandibular …

Vitamin D Signaling And The Impact On Mouse Mammary Gland Epithelium, Donald Grant Matthews

Legacy Theses & Dissertations (2009 - 2024)

A strong correlation between vitamin D deficiency and increased breast cancer incidence and mortality has been well established, leading researchers to further examine the possibility of using vitamin D in treatment and prevention strategies. Our long term goal is to elucidate the mechanisms by which vitamin D pathway signaling impacts on breast cancer. Generation of the high-affinity vitamin D receptor (VDR) ligand 1,25-dihydroxyvitamin D (1,25-D) from 25-hydroxyvitamin D (25-D) is mediated by CYP27B1 which is present and developmentally regulated in multiple tissues including the mammary gland. We utilized transgenic mouse models combined with diet-induced vitamin D deficiency to determine whether …

Using A Novel Multiplexing Method To Track Cell Populations And Cytodifferentiation During Development Of The Submandibular Salivary Gland, Charles Thomas Manhardt

Legacy Theses & Dissertations (2009 - 2024)

The development of submandibular salivary glands is complex and requires coordination of specific signaling events. Submandibular salivary glands originate as an epithelial invagination into the adjacent mesenchyme that leads to a single stalk and end bud; this end bud will go through a clefting process. Numerous rounds of clefting will lead to a fully developed salivary gland by this process, which is known as branching morphogenesis. As the gland undergoes morphogenesis, specific cues leading to differentiation of multiple cell types and even epithelial sub classes are required. By the later stages of development the glands are fully innervated, have an …

The Postsynaptic Regulation Of Synaptic Strength In Drosophila, Daniel Michael Gertner

Legacy Theses & Dissertations (2009 - 2024)

Postsynaptic Ca2+ plays an important role in synaptic homeostasis and synaptic plasticity. Postsynaptic Ca2+ signals have been shown to regulate synaptic transmission at the Drosophila larval neuromuscular junction (NMJ), however, these signals have not been well characterized. This will explore how these signals regulate synaptic strength and what channels are involved. In previous lab experiments Ca2+ transients were observed during evoked and spontaneous release (Desai and Lnenicka, 2011). It was further demonstrated that a reduction in synaptic strength occurs following synaptic stimulation. It was hypothesized that the increase in postsynaptic Ca2+ following synaptic stimulation activates the gCS and causes a …

Computational Modeling-Driven Study Of Signaling Pathway Affecting Cleft Formation During Submandibular Salivary Gland Development, Shayoni Ray

Legacy Theses & Dissertations (2009 - 2024)

Branching morphogenesis is a conserved mechanism of mammalian organ development (salivary glands, lungs, mammary glands, pancreas, kidney, etc.), and has been a classic topic of study for generations of developmental biologists. During the process of tissue formation, several cellular and molecular and protein signaling events occur at successive stages enabling proper formation of tissue shape and structure. In order to provide a comprehensive understanding of the process of branching morphogenesis, we need a systems level approach to integrate multifactorial information. My overall global hypothesis is that multiple mathematical modeling approaches can be utilized to extract crucial cellular and tissue level …

Mouse Salivary Gland Development Requires Optimal Substrate Compliance, Sarah Beth Peters

Legacy Theses & Dissertations (2009 - 2024)

The embryonic mouse submandibular salivary gland (mSMG) is a classic model to study mechanochemical signals involved in morphogenesis and differentiation amongst multiple, interacting cell populations. Scaffold compliance is alters cellular phenotype, but little is known about the effects of compliance on organogenesis. The overall aim of this project was to demonstrate that the processes of salivary gland epithelial branching morphogenesis and differentiation require a compliant, in vivo-like environment and are disrupted outside of this range.