Developmental Biology Commons^™

Architects Of Mrna Fate: Molecular And Cellular Control Of P-Body Organization In The Drosophilia Melanogaster Female Germline, Samantha Milano

Dissertations, Theses, and Capstone Projects

Processing bodies (P-bodies) are cytoplasmic ribonucleoprotein condensates that regulate mRNA storage, translational repression, and decay. While the biochemical principles governing condensate assembly have been extensively studied in vitro, how P-body organization is established and dynamically regulated in vivo to control specific mRNA populations remains poorly understood. This dissertation investigated the molecular and cellular mechanisms that govern P-body architecture and function in the Drosophila melanogaster female germline. First, I identified the conserved LSm protein Trailer Hitch (Tral) as a central organizer of P-body architecture. Using quantitative confocal and super-resolution microscopy combined with chemical perturbations, I showed that Tral coordinates the …

Interplay Between Patterning And Morphogenesis During Zebrafish Embryonic Development, Chia-Teng Chang

Arts & Sciences Graduate Student Theses and Dissertations

Patterning and morphogenesis occur concurrently during embryonic development. In many contexts, both processes are regulated by morphogen signaling: morphogens specify spatially organized cell identities while also influencing the cell behaviors that shape tissues. This creates a reciprocal problem. Morphogen signaling can affect how cells move, while cell movement can change how cells experience and interpret morphogen signals. This dissertation investigates this reciprocal problem during zebrafish gastrulation and neurulation. First, it examines how the ventral-to-dorsal bone morphogenetic protein (BMP) activity gradient regulates germ-layer morphogenesis during gastrulation. BMP signaling is known to pattern dorsal–ventral cell fate and regulate mesodermal convergence and extension …

Genetic Regulation Of Uterine Organogenesis, Diana A. Machado

Dissertations and Theses (Open Access)

In eutherian and marsupial mammals, the site of embryo implantation and gestation is the uterus. The precursor tissue of the uterus, oviducts, cervix, and upper vagina is the Müllerian duct epithelium and its adjacent mesenchyme. Morphological uterine variation between species is established during embryogenesis by species-specific differences in Müllerian duct fusion at the midline, growth, and differentiation. For example, laboratory mice have a bipartite uterus with two uterine horns and a single cervix, whereas humans have a simplex uterus with a single chamber and single cervix. In humans, variations in the fusion process can alter typical uterine morphology, correlating with …

Transcriptional Regulation In The Uterine Luminal Epithelium, Evelyn A. Carrion

Dissertations and Theses (Open Access)

Transcriptional Regulation in the Uterine Luminal Epithelium

Evelyn A. Carrion

Advisor: Richard R. Behringer, PhD

Abstract

The uterus is an organ comprised of multiple tissues that are essential for women’s health and reproduction. The uterus is composed of multiple tissue layers, including the perimetrium, myometrium, and the endometrium. The endometrium is the inner lining of the uterus, and contains the luminal epithelium, glandular epithelium, and stroma. The luminal epithelium is a simple columnar layer of cells that is necessary for embryo implantation. The uterus is derived in part from the embryonic precursor tissue called the Müllerian duct. There are no …

Regulation Of Müllerian Duct Mesenchyme Transcription During Mammalian Sex Differentiation, Haowen Li, Richard R Behringer, Rachel D Mullen

Dissertations and Theses (Open Access)

Sp7/Osterix (Osx) encodes a zinc-finger transcription factor of the Specificity-protein family discovered by Nakashima et al. at the MD Anderson Cancer Center. While primarily recognized for its role in osteogenesis, Osx has also been implicated in mammalian reproductive development, particularly in male sex differentiation, where Müllerian Duct (MD) regression occurs, mediated by anti-Müllerian hormone (AMH) signaling. AMH-induced regression signals are transduced by the mesenchymal tissue surrounding the ductal structure, known as the Müllerian Duct mesenchyme (MDM). It was discovered that AMH signaling is necessary and sufficient for driving Osx expression in MDM. A previous transgenic mouse reporter …

Comparative Assessment Of Developmental Fidelity In Hpsc-Derived Neural Crest Cells, Michael H. Zepeda

Electronic Theses, Projects, and Dissertations

Neural crest cells (NCCs) are a transient, multipotent cell population that contributes to craniofacial structures, peripheral neurons, melanocytes, and smooth muscle. Defects in NCC development underlie a broad range of congenital disorders known as neurocristopathies. Human pluripotent stem cell (hPSC)-derived NCCs provide an evaluable model for studying early human development; however, existing differentiation protocols produce variable outcomes, and no standardized method consistently generates high-fidelity NCC populations. To address this challenge, we compared five published hPSC-to-NCC differentiation protocols using the H9 human embryonic stem cell line. We hypothesized that specific protocols more faithfully recapitulate neural crest development through coordinated regulation of …

Junctional Actin As A Mechanical Hub For Supracellular Actomyosin Force Transmission During Apical Constriction, Jasneet Brar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apical constriction is a conserved morphogenetic mechanism that drives epithelial folding during development. During ventral furrow formation in Drosophila melanogaster, contractile actomyosin networks generate forces that reduce apical cell area resulting in tissue invagination. For these cell-scale forces to produce coordinated tissue-scale changes, contractile networks must be mechanically integrated across neighboring cells. Although adherens junctions are known to mediate this coupling, it is unclear how junctions are integrated into cortical actin cytoskeleton, which directly determines cell, and consequently tissue, shape. This thesis tests the hypothesis that supracellular actomyosin organization during apical constriction depends on distinct adherens junction based mechanical couplings: …

From Chaos To Clockwork: Investigating The Role Of Circadian Genes In Metabolic Development Of 2nd And 3rd Instar Drosophila Larvae, Elliott R. Ruegsegger, Stephanie Hood, Amy Poe

Biological Sciences Undergraduate Honors Theses

Circadian clocks regulate daily physiological and metabolic rhythms across many organisms. In Drosophila melanogaster, the molecular clock involving period (per) and timeless regulates gene expression across 24-hour cycles. Circadian rhythms are well characterized in adult, mature organisms, but their emergence during early developmental stages remain poorly understood. In D. melanogaster, the circadian regulation of sleep and feeding rhythms emerges during the 3rd instar larval stage. This suggests that the circadian regulation of metabolism may also arise during this stage. Further, the metabolic consequences of circadian clock disruptions during this developmentally rich period remain unclear. This research aimed to …

Analysis Of Developmental Cardiogenic Processes Mediated By Fox And Zinc-Finger Transcription Factors, Rajnandani Katariya

All-Inclusive List of Electronic Theses and Dissertations

Cardiogenesis is a highly choreographed biological process requiring the precise integration of gene regulatory networks to govern cell division, fate determination, and spatial positioning. Disruptions in these mechanisms lead to congenital heart defects (CHDs), which affect approximately 1% of live births globally. Due to the evolutionary conservation of cardiac signaling pathways and the structural homologies between the Drosophila dorsal vessel and the early vertebrate heart tube, Drosophila melanogaster serves as a powerful model for dissecting the fundamental mechanisms of heart development. This dissertation investigates the molecular orchestration of cardiac development, specifically focusing on the roles of the transcription factors Jumu …

Reconstruction Of Fox Transcription Factor-Regulated Subnetworks Mediating Cardiac Progenitor Cell Divisions, Md Rezaul Hasan

All-Inclusive List of Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly worldwide, affecting approximately 1% of live births, corresponding to 1.35 million infants born with CHD each year, and remains a leading cause of infant mortality; therefore, it is urgent to understand the genetic and molecular mechanisms underlying CHD for advancing early diagnosis and treatment. Because many aspects of the Drosophila heart formation are highly reminiscent of vertebrate heart development, Drosophila melanogaster serves as a simple yet powerful model system for studying cardiac development and CHD. While at least eight Forkhead box (Fox) transcription factors (TFs) are required for proper cardiac …

Characterizing The Molecular Response Of Embryonic Zebra Finch To Acute Sound Playback, Saidat O. Adeniran-Obey Miss

All Theses

Auditory stimuli are important cues that influence developmental plasticity in animals and are important for development and adaptation to an ever-changing environment. In the zebra finch (Taeniopygia guttata), there is evidence of adaptive developmental reprogramming in response to a prenatal ‘heat call’. Embryos exposed to this heat call exhibit changes in growth rate post-hatch, increased heat resistance, and enhanced reproductive success at maturity. However, it has long been assumed that embryonic zebra finches cannot respond to sound due to the immaturity of their auditory system. These findings raise the critical question of whether late-stage zebra finch embryos can, …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Cleft Palate And The Coordination Of Wnt Signaling And Pax9 In Murine Palatogenesis, Landon Wyatt

Honors Theses

Cleft palate is a common craniofacial birth defect that arises when the molecular and morphogenetic events guiding secondary palate formation lose coordination during a narrow developmental window. In mice, successful palatogenesis requires the paired palatal shelves to grow vertically, elevate above the tongue, and fuse at the midline; disruption of any of these steps can result in clefting. Two important regulators of this process are canonical Wnt signaling and the transcription factor Pax9, both of which contribute to normal palatal mesenchymal growth and patterning during early development. This paper first examines whether altered Dkk1/Wnt signaling contributes to the Pax9-null palate …

Using The Flexon Approach To Rnai To Identify Essential Genes That Affect Gonadal Development In C. Elegans, Joyce S. Lefevers

Undergraduate Theses

To elucidate the molecular role of essential genes in the gonadal development of Caenorhabditis elegans (C. elegans) it is necessary to utilize specialized molecular techniques such that the phenotypic effects of gene knockdown can be studied while the viability of the organism is preserved. Shaffer and Greenwald (2022) developed the floxed exon (flexon), a tool that improves upon previous approaches to spatiotemporal control of gene expression. The flexon subunit is made up of an artificial exon with a stop cassette flanked by artificial introns which, when inserted into a gene of interest, prevents the expression of that gene. …

Quantification Of Mouse Tracheal Epithelial Cell Differentiation With Cilia Defects, Olivia V. Allen

Honors Thesis

Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder that affects 1 in every 7,500 live births. PCD results from motile cilia defects, impairing mucociliary clearance and causing chronic respiratory infections. Our lab studies include three PCD mouse lines — bgh (Spef2), nm1054 (Cfap221), and Cfap54^gt/gt (Cfap54). Prior transcriptomic data led us to hypothesize that PCD mutant mouse tracheal epithelial cells (MTECs) exhibit reduced differentiation into ciliated cells. MTECs from the trachea of the Wild Type (WT) and the PCD mutant mouse lines were cultured at an Air Liquid Interface (ALI) to start …

Inside 'N Out: Etv2 Specification Of Hemangiogenic Lineages From Flk1+ Mesoderm, Dereck Antonio Shakeel Alleyne

Arts & Sciences Graduate Student Theses and Dissertations

The cardiovascular system is generated by mesodermal progenitors that give rise to endothelial, hematopoietic and muscle (smooth muscle and cardiomyocyte) lineages. Although vascular endothelial growth factor (VEGF), its receptor, FLK1/KDR and the transcription factor ETV2 are critically required for hemangiogenic specification, Flk1 and Etv2 expression has been observed in other mesodermal derivatives. During gastrulation, mesodermal progenitors are specified to contribute to the cardiovascular system; however, the early divergence of hemangiogenic and muscle progenitors, and their shared marker expression, complicates identification of common mesoderm progenitor populations contributing to both lineages. In this dissertation, I demonstrate how Flk1+ and Etv2+ lineage relationships …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

Decoupling Of Reproduction And Lifespan Trade-Off In Caenorhabditis Elegans Through Microbial Programming, Nora M. Villafuerte

LSU Master's Theses

The microbiome is increasingly recognized as a major regulator of host physiology. Using the Caenorhabditis elegans model, we investigated how natural commensal bacteria modulate host reproduction and lifespan through internal egg hatching, a phenotype in which retained embryos hatch within the maternal body. Screening strains from the CeMbio collection identified four focal strains Ochrobactrum BH3, Lelliottia JUb66, Pantoea BIGb0393, and Enterobacter CEent1 that significantly increased internal egg hatching during the late reproductive period. This contrasts with pathogenic bacteria, which induce early-onset internal egg hatching. Across the focal strains, worms exhibited reduced total brood size but an expanded reproductive window relative …

Effect Of Mid-Range Ultraviolet Light On Avian Embryonic Development, Keelie Hughes

Biology Theses

While it is a known fact that specific environmental conditions must be met to ensure proper embryonic development, the impact of changes in this delicate balance is unclear. Ultraviolet (UV) light has a narrow range of effectiveness in mature tissue, where too little can hinder molecular signaling and too much can cause damage to genetic material. This study exposed in ovo chicken embryos in the preliminary stages of development to mid-range UV radiation to examine developing embryo and tissue morphology using anthropometric methods and comparing proliferative cells among embryos exposed to varying doses of UV light. Additionally, quantitative polymerase chain …

Fgf Signaling Is Necessary For Newt Lens Regeneration, Leo Alexander Napoleon

Honors Theses and Capstones

The Iberian ribbed newt Pleurodeles waltl can regenerate the lens by transdifferentiating iris pigmented epithelial (IPE) cells into lens epithelial cells (LECs), but the mechanism by which this occurs remains largely uncharacterized. We aim to mechanistically show an early and critical role for FGF signaling by using small molecules to inhibit FGF receptors and observe the histological and intracellular effects. Two inhibitors were found to completely stall lens regeneration. Cell cycle analysis revealed decreased DNA synthesis and uniformly low but unchanged entry to mitosis under signaling inhibition by staining for EdU incorporation and phospho-histone H3 (pH3), respectively. Western blot revealed …

Comparing The Differences Of Hsp90Α And Hsp90Β In Native Protein Complex Incorporation, Daryna Serediuk

Honors Theses and Capstones

Epichaperomes are long-lasting, stable assemblies of chaperones, co-chaperones, and associated factors that facilitate cell survival in maladaptive cellular states. Their inhibition has emerged as an attractive therapeutic strategy for the treatment of cancer and neurodegenerative diseases (Rodina et al., 2016). Epichaperomes are hallmarks of robust proliferation in cancer cell populations across many cancer types and are abundantly present in several stem cell varieties, including induced pluripotent stem cells, human embryonic kidney cells, and cancer stem cells (Kishinevsky et al., 2018).

The core protein of the eukaryotic heat shock protein machinery, Heat Shock Protein 90 (Hsp90), is a central chaperone that …

Tmem116 Crispr-Mediated Knockout Prevents Proper Lens Regeneration In Iberian-Ribbed Newts, Damien T. Mann

Honors Theses and Capstones

Eye diseases like cataracts, age-related macular degeneration (AMD), and glaucoma are widespread and detrimental conditions affecting many people across the globe. While there are reliable and successful treatments for those with cataracts that can reverse vision impediments, others like glaucoma and AMD have limited treatment options. Additionally, eye damage resulting from these conditions is commonly irreversible, establishing a need for new treatment options. The Iberian-ribbed newt, Pleurodeles waltl, is a salamander species primarily studied for their amazing regenerative capabilities. Particularly, these newts are capable of de novo lens regeneration after a complete resection, providing a unique opportunity to study regeneration …

The Role Of Tumor Microenvironment In Glioblastoma Multiforme(Gbm) Therapeutic Resistance, Kwesi E. Taylor

Master's Theses or Doctor of Nursing Practice

Despite significant advances in cancer research and treatment, Glioblastoma multiforme (GBM) remains one of the most difficult cancers to treat effectively, with minimal improvement in long-term survival rates over the past few decades. This is largely attributed to tumor heterogeneity and the ability of tumor cells to develop adaptive resistance mechanisms supported by the tumor microenvironment (TME). Although the TME is recognized as a key contributor to tumor progression and therapeutic resistance, the underlying molecular pathways and regulatory genes remain incompletely understood. This study investigated the role of the tumor microenvironment in GBM therapeutic resistance using a bioinformatics approach. Single-cell …

How Semiflightless Birds Adapt: A Survey From Barú, Costa Rica, Eli P. Laloudakis

Scripps Senior Theses

When we think of birds, we think of flight. Because of this, scientific research often focuses on how birds evolved flight and how their wings function during flight. However, not all birds can fly or fly well, as wings wax and wane on developmental, seasonal, and evolutionary time scales (Dial and Heers 2021). Consequently, rudimentary wings can be found in developing birds, secondarily flightless or semiflightless birds, birds that undergo simultaneous molts, and extinct theropods with “protowings” (structures that preceded fully functional wings). Secondarily flightless and semiflightless birds often evolve where there is no/low predation, abundant year-round food supply, and …

Analyzing Early Medieval Perspectives Of Fetal Development, Nivedha Srinivasan

Honors Undergraduate Theses

This thesis examines early medieval perspectives of fetal development by analyzing two manuscripts: British Library, Cotton Tiberius A III and Leiden University, Vossianus lat. Q69. This study will investigate how knowledge of pregnancy was shared throughout England before the establishment of universities. Interest in medieval reproductive language has piqued in importance in recent years, especially due to modern legal debates surrounding reproductive rights. By examining descriptions of the nine months of fetal development in these two manuscripts, as well as in widely known earlier medical texts like Pliny’s Natural History and Vindicianus’ Gynaecia, this research explores how monastic writers in …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Modeling Inherited Retinal Disease In Zebrafish, Meet Patel

Theses and Dissertations--Biology

Inherited retinal diseases (IRDs) affect millions of people worldwide. Majority of IRDs are caused by degeneration of rod and cone photoreceptor cells (PRCs) due to gene mutations. The overarching goal of my dissertation is to model and evaluate the molecular role of various gene candidates involved in IRDs such as cone rod dystrophy (CRD) and retinitis pigmentosa (RP).

Mutations in CDHR1, a photoreceptor specific cadherin have been associated with CRD and recapitulated in mouse CDHR1 knockouts. However, the molecular function of CDHR1 remains unknown. CDHR1 has been shown to localize at the leading edge of murine rod nascent outer segment …

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 …

Epigenetic Modifications In Dedifferentiated Liver Cells To Restore Lost Liver Function, Shreya Sharma

Masters Theses

The goal of the study is to investigate whether the epigenetic modifications can enhance the restoration of liver gene expression in dedifferentiated hepatoma cells or not. For the study, we used dedifferentiated H11 hepatoma cell lines which overexpress one of a panel of introduced candidate liver-enriched transcription factors H11-HNF1a, H11-CREB3L3, H11-CREG1, H11- HHEX, H11-HNF6, and H11-IGFBP1. The cells were treated with the DNA methyltransferase inhibitor 5-azacytidine and the histone deacetylase inhibitor sodium butyrate, both individually and in combination. Gene expression analysis was determined by RT-qPCR, which revealed that while transcription factor overexpression alone produced limited activation, epigenetic modulation, particularly Histone …

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, …