Developmental Biology Commons^™

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 …

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 …

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 …

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 …

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, …

Patterns Of Ovarian And Gonadotropin Hormones In Emerging Adult Oral Contraceptive Users, Summer Mcormond

Undergraduate Research Posters

Oral contraceptives (OCs) are often initiated during adolescence and emerging adulthood, a period of continued maturation of the hypothalamic–pituitary–gonadal (HPG) axis. Because hormonal exposure during this window may shape emotional, biological, and reproductive outcomes, it is important to understand the specific formulations young women take and the hormonal profiles these formulations produce. This study characterizes OC formulation features and measured hormone levels in young adult OC users (n = 30).

Ethinyl estradiol (EE) doses ranged from 0.01–0.035 mg (mean = 0.022 mg), with 70% using ≤0.02 mg. Pill regimens included 21/7 packs (83%), 24/4 packs (10%), and 84/7 regimens (3%). …

Context Dependent Regulation Of Dicer Function During Oocyte-To-Embryo Transition, Nick A. Newkirk

Dissertations and Theses (Open Access)

Over two decades ago, Dicer was discovered as the primary enzyme responsible for the generation of small RNAs known as the microRNAs (miRNAs) and short interfering RNAs (siRNAs). Spatiotemporal regulation of Dicer-dependent small-RNA biogenesis affects many aspects of biology, including aging, disease progression, fertility, and cancer. Interestingly, a distinct population of Dicer-dependent small RNAs, known as the endogenous siRNAs (endo-siRNAs), are uniquely abundant in the germ cells and gametes, and are critical for normal fertility. Despite their function regulating new life, the mechanisms controlling their biogenesis and subsequent germ cell functions remain poorly defined. Work to parse these mechanisms in …

Stayin' Alive (Even Without Oxygen): Retinal Development In Austrofundulus Limnaeus, Carmen Zecilia Rodriguez

Dissertations and Theses

The vertebrate eye is one of the most metabolically active organs in the body and is particularly sensitive to environmental stressors such as oxygen deprivation. Understanding how eye development proceeds under such conditions can provide critical insights into mechanisms of cellular resilience, tissue organization, and developmental plasticity. The annual killifish Austrofundulus limnaeus represents a unique model for investigating these processes due to its remarkable tolerance to anoxia during embryogenesis. However, the wild-type form is heavily pigmented, limiting the effectiveness of traditional imaging techniques for studying eye development. This thesis characterizes eye development and anoxia resilience in both wild-type and melanin-deficient …

Centrosomal And Non-Centrosomal Microtubule Networks Coordinate To Drive Nuclear Dynamics In Developing Epithelium, Rashmi Budhathoki

Electronic Theses and Dissertations

The morphogenesis of developing tissues relies on extensive cellular rearrangements in shape, position, and identity. A key process in reshaping tissues is cell intercalation-driven elongation, where epithelial cells align and intercalate along a common axis. Typically, analyses focus on how peripheral cortical forces influence cell shape changes. Less attention is given to how inhomogeneities in internal structures, particularly the nucleus, impact cell shaping. Here, we examine how pulsed contractile and extension dynamics interact with the nucleus in elongating Drosophila embryos. Our data show that tightly packed nuclei in apical layers hinder tissue remodeling/oscillatory behaviors. We identify two mechanisms for resolving …

Analysis Of An Ethanol Sensitive Bmp-Nkx2.3-Fgf Signaling Pathway In Pouch Morphogenesis., Hieu Dai Le Vo

Electronic Theses and Dissertations

Craniofacial malformations lie at the heart of Fetal Alcohol Spectrum Disorders (FASD). While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Bone Morphogenetic Protein (Bmp) signaling pathway dependent pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3 and Fibroblast Growth Factor (Fgf) signaling, may mediate the impact of ethanol on Bmp mutants. Here, I …

Breaking The Rules: Post-Translational Modifications And Proteome Dynamics During Anoxia, Chelsea Jordan Hughes

Dissertations and Theses

Most organisms are ill-equipped to survive anoxia, but some organisms have developed molecular strategies to mitigate the cellular stressors associated with a lack of oxygen. While it is established that anoxic survival is contingent on metabolic suppression, it is unclear what mechanisms support this change in gene expression. Gene expression is regulated by a variety of mechanisms within the cell, including alteration of chromatin structure through histone modifications and protein modifications which contribute to the ever-changing proteomic landscape of the cell. Protein modifications such as ubiquitylation can lead to the degradation of proteins, while modifications to transcription factors can change …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie

LSU Doctoral Dissertations

Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …

Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

This project aims to create CRISPR-CAS9 mutations in the APETELA3 (AP3) gene of the model plant Arabidopsis thaliana. AP3 is a class B gene critical to the petal and stamen development of Arabidopsis flowers. AP3 is defined in a MADS domain, which binds directly to DNA and may be responsible for the expression of the CaRG-box genes. AP3 works in conjunction with PISTILLATA (PI), AGAMOUS (AG), APETALA1 (AP1), and SEPALLATA (SEP) genes to specify the development in the second and third whorls of the flower. While several alleles of AP3 already exist, these alleles are strong alleles that knockout gene …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

Expression And Function Of Floral Symmetry Genes In The Regulation Of Flower Shape In Fedia Graciliflora, Theresa A. Mustacchio

Theses and Dissertations

Shifts between radial symmetry (actinomorphy) and bilateral symmetry (zygomorphy) in flowers have occurred multiple times independently within angiosperms (flowering plants). Evidence across angiosperms indicate the transcription factors RADIALIS (RAD), DIVARICATA (DIV), and CYCLOIDEA (CYC) play a major role in regulating floral symmetry and morphology. The CYC-like genes have been shown to shift their expression dorsally independently in nearly all shifts to bilaterally symmetrical flowers examined. Three core eudicot clades of CYC-like genes have been identified: CYC1, CYC2 and CYC3, with only CYC2 genes being shown to have a role in floral symmetry. We use the non-model plant, Fedia graciliflora (Caprifoliaceae) …

Cdh-3/Cadherin, Yap-1/Yap And Egl-44/Tead Promote Syx-2/Syntaxin And Eff-1 Fusogen-Mediated Phagosome Closure, Alec Whited, Aladin Elkhalil, Ginger Clark, Piya Ghose

Biology Theses - Archive

Physical interactions between cells, such as cell-cell junctions, can profoundly impact cell fate. A vital cell fate for normal development and homeostasis is programmed cell death. Cells fated to die must be efficiently cleared away via phagocytosis, and defects are associated with a variety of diseased states. Whether cell-cell physical associations affect programmed cell elimination has not been well-explored. Here we describe, in vivo, a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance during development. We previously described the specialized cell death program “Compartmentalized Cell Elimination” (CCE) in the C. elegans embryo. During CCE, the tail-spike cell (TSC), a …

Temporal Dynamics Of Programmed Genome Rearrangement In Sea Lamprey Embryogenesis: A Deep Learning & Lightsheet Imaging Approach To Studying Early Developmental Transitions, Kasturi Rajandran

Theses and Dissertations--Biology

Programmed genome rearrangement (PGR) in the sea lamprey (Petromyzon marinus) leads to the elimination of ~0.5Gb (20%) of the germline genome during early embryogenesis, yet its timing relative to the maternal-to-zygotic transition (MZT) remains unclear. In this study, we imaged embryos cleared at 3-hour intervals (up to 72 hours post fertilization (hpf)) using high-resolution lightsheet fluorescence microscopy and a custom deep-learning image-analysis pipeline (~80% accuracy) to quantify nuclei and micronuclei counts. Micronuclei, which are the hallmarks of PGR first appear between 24 to 27hpf (vs ~36hpf previously reported) indicating PGR starts earlier than previously reported in the sea …

Investigation Of Reproductive Inhibition During Chronic Heat Stress In C. Elegans, Macy Makenna Nielander

Theses and Dissertations

Nearly all organisms experience heterogeneity in environmental conditions that can negatively impact fitness. A common adaptive strategy to reduce the impact of this stress is called facultative diapause, where development and reproduction are temporarily arrested to promote survival. Facultative diapause is characterized by three major criteria, the arrest must be (i) induced by an unfavorable environmental condition, (ii) reversible, and (iii) driven by genetically regulated mechanisms. The aim of this thesis was to determine whether chronic heat-induced inhibition of egg laying in Caenorhabditis elegans represents a novel form of facultative diapause. It was found that the inhibition of egg-laying is …

Soxb1 Transcription Factors Are Essential For Initiating And Maintaining Neural Plate Border Gene Expression, Elizabeth Schock, Joshua R. York, Austin P. Li, Ashlyn Y. Tu, Carole Labonne

Markey Cancer Center Faculty Publications

SoxB1 transcription factors (Sox2/3) are well known for their role in early neural fate specification in the embryo, but little is known about functional roles for SoxB1 factors in non-neural ectodermal cell types, such as the neural plate border (NPB). Using Xenopus laevis, we set out to determine whether SoxB1 transcription factors have a regulatory function in NPB formation. Here, we show that SoxB1 factors are necessary for NPB formation, and that prolonged SoxB1 factor activity blocks the transition from a NPB to a neural crest state. Using ChIP-seq, we demonstrate that Sox3 is enriched upstream of NPB genes in …

Adipose-Derived Mesenchymal Stem Cells And Their Derived Epidermal Progenitor Cells Conditioned Media Ameliorate Skin Aging In Rats, Mohamed M. Kamal, Omar Ibrahim Badr, Tasnim Mahmoud

Pharmacy

BACKGROUND: Skin alterations are among the most prominent signs of aging, and they arise from both intrinsic and extrinsic factors that interact and mutually influence one another. The use of D-galactose as an aging model in animals has been widely employed in anti-aging research. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are particularly promising for skin anti-aging therapy due to their capacity for effective re-epithelization and secretion of various growth factors essential for skin regeneration. Accordingly, we aimed to examine the potential utility of Ad-MSCs as a therapy for skin anti-aging. METHODS: In this study, we isolated and characterized adipose-derived mesenchymal …

The Role Of Edc3 In Drosophila Melanogaster Neuronal Development, Keelan Zius

Electronic Theses and Dissertations

Enhancer of mRNA-decay 3 (Edc3) is a component of multiple decapping complexes that regulates the transcriptome by targeting a subset of transcripts for decapping for 5’-to-3’ messenger RNA (mRNA) decay. A missense mutation in the conserved Lsm domain of Edc3 has been reported in two siblings presenting with mild, non-syndromic intellectual disability (ID), however, the role of Edc3 is neuronal development has never been evaluated. Here, we use the Drosophila melanogaster model system to investigate the effects of Edc3 disruption on neuronal development. We found Edc3 reduction leads to significant hyperplasia at the larval neuromuscular junction (NMJ), providing the first …

Morphological Remodeling Of The Endoplasmic Reticulum During Mitosis And Its Influence On The Integrity Of The Spindle Apparatus, Katie R. Rollins

Electronic Theses and Dissertations

The Endoplasmic Reticulum (ER) is the largest organelle in the cell by surface area and forms contacts with other organelles throughout the cell. In recent work, the ER has been implicated in numerous processes within the cell beyond its canonical roles of protein synthesis and calcium storage. The ER also undergoes a remarkable transition in morphology during cell division, with mitotic divisions requiring a massive remodeling of various membranous organelles such as the nuclear envelope and Golgi. However, whether changes in ER behaviors modulate mitotic events is less clear. The rapid cleavage divisions in the early Drosophila embryo are a …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

The Impact Of Mutations In The Arabidopsis Apetela (Ap3) Gene, Hazel R. Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

The purpose of this research is to understand the molecular functioning of the Arabidopsis thaliana Apetela (Ap3) gene. We created mutations in two sites of the gene, AP3-3 and AP3-5. These are predicted to change AP3 protein structure, which may result in a mutated flower. Analyzing the effects of new mutations allows an understanding of protein formation both in plants and humans.

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …