Developmental Biology Commons^™

Causes And Consequences Of Mitotic Chromosome Missegregation In Human Pluripotent Stem Cells, Chenhui Deng

Dartmouth College Ph.D Dissertations

Mitosis is a fundamental process that ensures the equal distribution of replicated chromosomes, which carry an organism's genetic material, into two daughter cells. The fidelity of mitosis is paramount, as errors in chromosome segregation result in aberrant chromosome numbers, including gains or losses, a state termed aneuploidy. Aneuploidy impacts a broad range of human conditions, including being one of the major hurdles in early human development where it is the primary cause of miscarriages and birth defects. Strikingly, more than 70% of human preimplantation embryos are aneuploid with mitotic chromosome segregation errors being the most common source of aneuploidy. However, …

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 …

Investigating The Regulation Of The Hypothalamic-Pituitary-Interrenal Axis In Atlantic Sturgeon (Acipenser Oxyrinchus) Following An Acute Stressor, Liam Doherty

Undergraduate Theses, Capstones, and Recitals

This study investigated the response to acute stress in Atlantic sturgeon (Acipenser oxyrinchus) and HPI axis regulation of glucocorticoid production during stress by examining the expression of key genes― corticotropin-releasing hormone (crh), corticotropin-releasing hormone receptor (crhr), proopiomelanocortin (pomca/pomcb), melanocortin 2 receptor (mc2r), and steroidogenic acute regulatory protein (star)―that are associated with hypothalamus/pituitary/interrenal (HPI) axis of bony fishes. Additionally, tyrosine hydrogenase (th1 and th2) and phosphoenolpyruvate carboxykinase (pepck), found in catecholamine-producing cells in the head kidney of the sturgeon, were investigated …

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 …

High Mdmx (Mdm4) In Mutant P53 Expressing Breast Cancer Cells Activates The Cxcl12-Cxcr4 Metastasis Signaling Axis, Rusia H. Lee

Dissertations, Theses, and Capstone Projects

The metastasis-promoting G-protein coupled receptor (GPCR) CXCR4 is activated by the cytokine CXCL12 (also known as SDF-1) to promote metastasis through CXCR4 upregulation. High CXCR4-expressing cancer cells utilize CXCL12, the exclusive endogenous ligand of CXCR4, to intravasate into the blood as circulating tumor cells (CTCs) which then extravasate to distant metastatic sites. We previously determined the oncogenes, Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX), drive TNBC metastasis and positively correlate with high expression of CXCR4. Interestingly, this upregulation of CXCR4 was only observed in primary tumor cells grown in the tumor microenvironment …

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 …

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Regulation Of Intracellular Sorting Of The Bruno Protein In Drosophila Flight Muscles, Travis Main

Master's Theses

Understanding mechanisms of intracellular sorting is a fundamental inquiry of cell biology. We used the B-body and protein Bruno (Bru) as a model to study the formation of nuclear domains that are membraneless organelles inside the cell nucleus. Specifically, we sought to identify protein sequences that regulate Bru's affinity to B-bodies and protein aggregation. We generated various Bru mutants and subsequently tested them in vivo using fluorescence microscopy. We found that the protein solubility of Bru is determined through an interplay of RNA recognition motifs (RRMs) and intrinsically disordered regions (IDRs). Using truncation analysis, we identified a 31-amino acid region …

The Effect Of Diabetes Mellitus On Differentiation Of Mesenchymal Stem Cells Into Insulin-Producing Cells, Mohamed M. Kamal, Omar I. Badr, Shohda A. El-Maraghy, Heba R. Ghaiad

Pharmacy

Background

Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods

We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and …

Characterization Of Mitochondrial Morphology In Drosophila: Early Embryogenesis Description Via Confocal Microscopy, Kendall Miller

Biological Sciences Undergraduate Honors Theses

Mitochondria are not static organelles, but instead are dynamic networks that undergo rapid changes in subcellular distribution, organization, and activity in response to external stimuli. Notably, mitochondria can undergo fission and fusion, collectively known as mitochondrial dynamics. Mitochondrial fusion creates assembled networks of mitochondria that are maximally efficient at generating ATP through oxidative phosphorylation. Conversely, mitochondrial fission leads to network fragmentation and a shift towards glycolysis, which is the dominant mode of ATP generation in oxygen-limiting and stressed conditions. While mitochondrial dynamics have been intensively studied in isolated cells under stressful conditions, much less is known about how mitochondria behave …

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 Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Role Of Atp-Binding Cassette (Abc) Transporters As A Protector Of Testis Stem Cell Niche From Chemotherapy Drugs In Drosophila Melanogaster, Swagata Maity

Master's Theses

In chemotherapy treatments most tumor cells are destroyed by drugs, but some tumor cells are drug resistant, and these are known as cancer stem cells (CSCs). Normal adult stem cells are also chemo resistant. Therefore, investigation of normal stem cells can be useful to provide further knowledge of CSCs. One of the primary ways that CSCs achieve drug resistance is by drug efflux through transmembrane pumps called ATP-binding cassette (ABC) transporters. Many studies on ABC transporters have been performed in vitro using cultured cell lines, but very few studies have been performed on normal stem cell populations in vivo. Drosophila …

The Study Of Dmrt1 In Zebrafish And How It Impacts Sex Determination, Raymond Michael Poirier

Graduate Masters Theses

The dmrt1 gene is common amongst most animals and functions to determine or maintain male sex during development. Similarly, in zebrafish dmrt1 is important for male sex determination and maintaining proper testis morphology. This gene is expressed in two different cell types of the testis in zebrafish, germ cells and Sertoli cells. While we know where this gene is expressed and what its role is, it is not known if it is sufficient to drive male fate. If so, then in which cells is it sufficient to drive male fate in the testis? I aimed to answer this question by …

Understanding The Role Of Minor Intron Splicing In Spermatogenesis, Jade Rosado, Kazumasa Takemoto, Rahul Kanadia

Honors Scholar Theses

The minor spliceosome is composed of the unique small nuclear RNAs (snRNA), U11, U12, U4atac, and U6atac, and is necessary for the splicing of less than 0.5% of introns, termed minor introns. Minor intron containing genes (MIGs) regulate diverse processes, one of which is spermatogenesis. Specifically, 111 testis-specific MIGs have been identified, suggesting that minor splicing is necessary for spermatogenesis. To interrogate the role of minor splicing in spermatogenesis, we conditionally ablated the Rnu11 gene, which encodes for the U11 snRNA, in the developing testes via Stra8-iCre, creating a Rnu11^Flx/Flx::Stra8-Cre⁺ mutant. We found, at postnatal …