Cell and Developmental Biology Commons^™

Uncovering Novel Small Regulatory Rna In Protostome, Sweta Khanal

Dissertations

Small RNAs play pivotal roles in post-transcriptional gene regulation across diverse phylum of protostomes. In this study, we investigate the functional significance of atypical miRNAs, mirtron miR-1017 in Drosophila. Through ectopic expression in neuronal cells, we demonstrate that miR-1017 extends lifespan by targeting its host transcript, acetylcholine receptor Dα2, and influencing its splicing. This novel trans-regulatory function suggests a mechanism for mirtron evolution, highlighting the interplay between splicing and post-transcriptional regulation. Additionally, we profile small RNA populations in the polychaete developmental model Capitella teleta, shedding light on the small RNA landscape in annelid worms. Our analysis reveals a rich …

Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah

Electronic Thesis and Dissertation Repository

Myogenesis is defined as the formation of skeletal muscle tissue during embryonic development and involves a multitude of cellular signalling pathways. Among these include the Sonic hedgehog (Shh) signalling pathway which must be deactivated for differentiation into muscle cells to occur. However, less is known regarding the pathways operation during cell differentiation and whether Suppressor of Fused (SUFU), the protein inhibitor of Shh signalling, plays a role. To address this, mouse C2C12 myoblast cells were utilized as a model and differentiated into muscle cells to identify the presence of SUFU during this time. Experiments in qRT-PCR show a decrease in …

Genetic Regulation Of Müllerian Duct Regression, Malcolm Moses

Dissertations & Theses (Open Access)

Mammals, including humans, develop progenitor tissues for both male and female reproductive tract organs before they fully differentiate into a male or female tract. The progenitor tissue for the male reproductive tract is known as the Wolffian duct (WD), and the progenitor tissue for the female reproductive tract is the Müllerian duct (MD). The WD further differentiates into the vas deferens, epididymis, and seminal vesicle, while the MD differentiates into the oviduct, uterus and upper vagina. An essential step in sex differentiation for males is the regression of the MD. This regression initiates with anti-Müllerian hormone (Amh) transcription …

An Analysis Of The Involvement Of Toll Receptors In Cell Movements During The Elongation Of Tribolium Castaneum, Kathryn Russell

Senior Theses and Projects

Elongation of the anterior/posterior body axis is a critical part of embryonic development. Cell movements are known to play a significant role in embryo elongation in the red flour beetle Tribolium castaneum. In the arthropod model organism, Drosophila, Toll receptors have a demonstrated role in the elongation of the embryo by driving convergent extension, in which rows of cells intercalate with one another in one direction to extend tissue in the other. In Drosophila, Toll receptors are a link between anterior-posterior patterning genes expressed in discrete stripes and effector molecules causing cell movements. This cell movement is caused …

Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes

Electronic Thesis and Dissertation Repository

Pathogenic variants in the human PRR12 (Proline Rich 12) gene are associated with PRR12-related Neuroocular Syndrome. However, little is known about the gene/protein function. The zebrafish was utilized to address this, as its attributes place it as a premier model to study genes involved in human development and disease. In situ hybridization and RT-PCR of embryos and larvae, and qRT-PCR of adult tissues revealed the spatial and temporal distributions of the prr12 paralogues: prr12a and prr12b. Both paralogues were detected from the maternal and zygotic transcriptomes in a global and diffuse expression pattern, and there was enrichment …

Investigating The Role Of Chd7 And Sox11 In Retinal Cell Development And The Ocular Complications Of Charge Syndrome, Laura Krueger

Theses and Dissertations--Biology

Proper formation of the visual system requires the precise interaction of several embryonic cell lineages, including the neuroectoderm (forms the retina and retinal pigment epithelium), surface ectoderm (forms the lens), mesoderm and cranial neural crest cells (form the ocular blood vessels and anterior ocular structures). When this process is disrupted structural birth defects such as coloboma result, leading to pediatric visual deficits. Ocular developmental defects are often present in larger syndromic disorders. One example is CHARGE syndrome, a genetic disorder characterized by coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities, and ear abnormalities. Pathogenic variants in CHD7 have been …

The Effect Of Ethanol On Cellular Movements And Development In C. Elegans, Caitlin N. O'Connor

West Chester University Master’s Theses

Neural tube development, which gives rise to the central nervous system, is vital to embryonic development. Neural tube defects, like spina bifida, are serious and common congenital defects which can result in life-long medical complications. Folic acid has been used as a preventative measure for neural tube defects and has appeared to decrease the occurrences of neural tube defects. However, the mechanism behind folic acid’s role in neural tube development is unclear. Furthermore, some evidence suggests that ethanol decreases the levels of folates and folate coenzymes in the fetal brain and downregulates folic acid metabolism genes. To better understand the …

Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance, Kayla Titialii-Torres

Theses and Dissertations--Biology

Hundreds of millions of people are affected by diabetes worldwide. Whether they are diagnosed with prediabetes or Type I or II diabetes, there are a variety of mechanisms in the pathogenesis of diabetes. Diabetes is a disease which consists of recurring states of hyperglycemia that can be difficult to manage due to either lack of insulin production or improper utilization of insulin. While these mechanisms of action differ, complications induced by diabetes occur in both poorly regulated Type I and II. Common complications of diabetes include nerve damage, kidney damage, and eye damage. Eye damage specifically is called diabetic retinopathy …

Activation Of Nrf2 At Critical Windows Of Development Alters Protein S-Glutathionylation In The Zebrafish Embryo (Danio Rerio), Emily G. Severance

Masters Theses

Perturbation of cellular redox homeostasis to a more oxidized state has been linked to adverse human health effects such as diabetes and cancer. However, the impact of altering the regulation of redox homeostasis during development is not fully understood. Specifically, this project investigates the role of the Nrf2 antioxidant response pathway and its effect on glutathione (GSH; cellular redox buffer) at critical windows of development. To explore this, we used zebrafish embryos (Danio rerio) as a model due to the function of GSH and the Nrf2 being conserved among vertebrates. We exposed zebrafish embryos to three Nrf2 activators: two antioxidant …

The Role Of Tbx2 In Germ Layer Suppression And Dorsoventral Patterning During Early Vertebrate Development, Shoshana Reich

Dissertations, Theses, and Capstone Projects

The differentiation of the three primary germ layers is precisely regulated by inductive cues, the intracellular networks through which these signals are transduced, and a broad array of nuclear proteins, such as transcription factors and epigenetic modifiers. Precise regulation of these various factors is crucial to proper development. Members of the T-box family of DNA-binding proteins play a prominent role in the differentiation of the three primary germ layers. VegT, Brachyury, and Eomesodermin function as transcriptional activators, are expressed in the presumptive mesendoderm and, in addition to directly activating the transcription of endoderm- and mesoderm-specific genes, serve variously as regulators …

Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud

Theses and Dissertations

The serine/threonine kinase BRAF is a key part of the Ras-Raf-MEK-ERK pathway, an inducer of cell growth, differentiation, and survival. In humans, activating mutations, most commonly BRAF(V600E), have been detected in several cancers, including melanoma and thyroid cancer. In the Caenorhabditis elegans ortholog LIN-45, the equivalent mutation LIN-45(V627E) results in elevated Raf-MEK-ERK signaling. We performed an unbiased genetic screen to identify negative regulators of LIN-45(V627E). Here, we report the identification of the E3/E4 ubiquitin ligase UFD-2, and show it is a negative regulator of LIN-45 protein activity and levels. Loss of UFD-2 leads to accumulation of wild-type LIN-45 protein as …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

Rab35 Centered Membrane Trafficking Pathway Directs Apical Constriction During Drosophila Gastrulation, Hui Miao

Electronic Theses and Dissertations

Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating high-tension contractile forces at the cell cortex before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be cellular processes to extract unidirectional changes that drive processive transformations in cell shape. During Drosophila melanogastergastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a …

The Genome-Wide Roles Of The Lung Lineage Transcription Factor Nkx2-1 In The Regulation Of Opposing Cell Fates In Vivo, Danielle Renae Little

Dissertations & Theses (Open Access)

Lineage transcription factors mark, promote, and maintain multiple distinct cell types originating from a common progenitor. Despite their essential role, how such factors function and bind genome wide to orchestrate the epigenetic changes necessary to form and maintain these identities in vivo is unclear. One lineage transcription factor NK Homeobox 2-1 (NKX2-1) is expressed throughout the lung epithelium during development and was thought to be lost in the extraordinarily thin cell type required for gas exchange– the alveolar type 1 (AT1) cell. Complementing precise genetic knockouts with cell type-specific ChIP-seq, ATAC-seq, and scRNA-seq, our study shows that AT1 and AT2 …

The Role Of Cdx4 During Patterning Of Definitive Hemogenic Mesoderm, John Philip Creamer

Arts & Sciences Electronic Theses and Dissertations

The current standard of treatment for a variety of hematopoietic malignancies and genetic disorders is allogenic bone marrow transplantation, where donor hematopoietic stem cells (HSCs) engraft within the host and give rise to all of them hematopoietic lineages necessary for homeostasis. In many cases, finding a compatible human leukocyte antigen (HLA) matching donor is not possible, due to the large amount of genetic variation at those loci, but with the advent of induced pluripotent stem cells (iPSCs), unlimited sources of patient matched cells can be derived. Hematopoietic differentiations of human pluripotent stem cells (hPSCs) have been shown to recapitulate the …

Fgf20 In Olfactory System And Cochlea Development, Lu Morgan Yang

Arts & Sciences Electronic Theses and Dissertations

The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. We identified a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE and increase OE surface area. We show that these Fgf20-positive, epithelium-spanning progenitor (FEP) cells are responsive to Wnt/β-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny, and positively regulates Fgf20 expression. We further show that FGF20 signals to the …

Evaluation Of The Bax-Vdac Interaction And Their Influence On Apoptosis In Drosophila Melanogaster, Frances Marie Gatlin

Honors Theses

Apoptosis, also known as programmed cell death, is a cellular process used for development or for when cells undergo injury or stress. The Bcl2 family of proteins includes both pro-apoptotic and anti-apoptotic proteins that control the intrinsic pathway of apoptosis. Understanding the mechanisms and influence these proteins have on apoptosis is an important area of research focused on in Dr. Jones’s lab. Evidence shows a homology amongst the Bcl2 family of proteins at the BH3 domain. Dr. Jekabsons' lab has found a potential homology amongst VDAC 1-3 and the Bcl2 family at the BH3 domain.

Specifically, our lab is using …

Elucidating The Functional Location Of Platelet-Derived Growth Factor Receptor Alpha, Creation Of A Review Chapter On The Use Of Zebrafish In Studying Congenital Heart Defects, And Using 3d Printing To Create Laboratory Tools, Jaret Lieberth

Honors Theses

Congenital heart defects (CHDs) are currently the most prevalent form of birth defect in the United States. Their combined frequency and severity make necessary a deeper understanding of the molecular underpinnings guiding heart formation. The first major step in cardiac morphogenesis, cardiac fusion, involves the medial movement of bilateral populations of myocardial precursor cells to the embryonic midline, where they merge to form the primitive heart tube. Although crucial to subsequent organogenesis, the precise mechanisms governing cardiac fusion remain unknown. Previous studies have found that a mutation in platelet-derived growth factor receptor alpha (pdgfra), called refuse-to-fuse (ref), results …

Arid1a Haploinsufficiency Initiates Neural Crest Transformation In A Mouse Model Of Mycn-Driven Neuroblastoma, Kirby A. Wallace

Theses and Dissertations (ETD)

Mouse models of cancer are critical for developing therapeutic treatments for pediatric patients. Recent sequencing studies of neuroblastoma (NBL) patient tumors have uncovered precise deletions in the chromatin remodeler and tumor suppressor gene (TSG) ARID1A. Additional causal studies supported ARID1A’s candidacy as a putative 1p36 TSG in MYCN-driven NBL. This study aimed to causally test Arid1a loss during Mycn-driven NBL initiation through the development of a mouse model of high risk NBL.In this study, we modified a Mycn-driven mouse model of NBL to incorporate Cre mediated deletion of floxed Arid1a. Briefly, in freshly isolated embryonic day 9.5 primary trunk neural …

Characterizing The Requirements For The Matricellular Protein, Dccn, In Nervous System Function, Elizabeth L. Catudio Garrett

Graduate Student Theses, Dissertations, & Professional Papers

The brain is organized as a complex network of specialized neurons that communicate via a combination of electrical and chemical signals. Our brains function to generate movement, control organ function, or direct complex behaviors; all of which requires the ability to regulate the flow of communication between circuits and networks. Work in this thesis addresses two areas of neuron communication: first, how does the release of more than one neurotransmitter from a single neuron impact behavior, and second, are matricellular proteins (MCPs) key contributors to synaptic transmission and neuron function? The conserved CCN family of MCPs have a …

Characterizing Changes In The Colonic Epithelium Of Lrig3 Null Mice, Natalie Pedicino

Scripps Senior Theses

The lining of the colon, or colonic epithelium, is a very dynamic and highly regulated tissue in the human body. Colonic stem cells are a key component of this tissue, and they make up the stem cell niche, which is found at the base of the colonic crypt. Regeneration of the colonic epithelium, which occurs on a weekly basis, is a complex process, and proteins responsible for directing regeneration are still being discovered. Two critical regulatory proteins, Lrig1 and Lrig3, have been shown to modulate the EGFR pathway, a key signaling pathway for growth, differentiation, and regeneration. Data from the …

The Evolution And Development Of Chiropteran Flight, Emmaline Willis

Honors Theses and Capstones

No abstract provided.

Developmental Mechanisms For The Diversification Of Polyphenic Morphs In The Head Horn Of Onthophagine Beetles (Coleoptera: Scarabaeidae Onthophagus Taurus): Plasticity Through Nutrition, Logan Paul Zeigler

Graduate Theses, Dissertations, and Problem Reports

Developmental plasticity is the phenotypic variation between organisms that is caused by environmental interactions affecting the developmental systems of organisms. The research focused primarily on nutrition-responsive developmental plasticity. In this research we used the nutritionally determined head horn development of Onthophagus taurus to better understand the developmental mechanisms and genetic underpinnings of nutrition-responsive trait development. We focused specifically on altering the availability of specific nutrition-related primary metabolites, cholesterol and palmitic acid, identified in the activity of The Hedgehog pathway, a critical pathway in head horn development. By altering diet composition using cholesterol, reducing transcript expression of an acyltransferase gene, rasp …

The Effects Of Internal Physiology On Polyphenic Horn Development In The Dung Beetle Onthophagus Taurus, Naomi Garrett Williamson

Graduate Theses, Dissertations, and Problem Reports

An organism’s phenotype can be affected in development by alterations to gene expression based on environmental inputs. Nutrition is one such environmental input and the central regulator of development of large horn or small horn phenotypes in the dung beetle species, Onthophagus taurus. However, little is known about the nature of chemical compounds that are critical to this plastic horn development. To better understand these compounds, we are utilizing an untargeted metabolomic approach as well as a targeted gene approach. Through the metabolomic approach, it was uncovered that environmental conditions tend to have a greater impact on metabolomic composition …

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate …

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations & Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

The Role Of Xenopus Laevis Reck In Ecm Remodeling And Tissue Patterning, Jessica Willson

Electronic Thesis and Dissertation Repository

Proper cell-cell and cell-extracellular matrix (ECM) interactions are vital for cell migration and patterning of the vertebrate embryo. Matrix metalloproteinases (MMPs) and their inhibitors, reversion-inducing cysteine-rich proteins with Kazal motifs (RECK) and tissue inhibitors of metalloproteinases (TIMPs), are all differentially expressed during embryogenesis to regulate such ECM remodeling events and cell interactions. While TIMPs are a family of 4 secreted proteins that share overlapping substrate specificities of MMPs, RECK is unique in that it is a membrane-anchored MMP inhibitor that is embryonic lethal in mice. I used Xenopus laevis as a model organism to investigate the role of RECK as …

Patterns Of Morphological Plasticity In Metriaclima Zebra And Danio Rerio Suggest Differently Canalized Phenotypes Due To Form-Function Relationships, Dylan Jockel

Masters Theses

In order to ascertain the degree of compatibility in developmental restructuring and behavioral plasticity between two fish species frequently made subject of laboratory research (Metriaclima zebra & Danio rerio), alternative trophic niche exposure experiments utilizing novel three-prong feeding treatments were conducted to obtain morphometric data, which demonstrated both species do bear some degree of plasticity. The results are somewhat complicated by differences in locality of detectable restructuring, which may be due to disparity in the form-function relationship for each species’ lineage. Each is notable in the manner of respective species’ jaw protrusion, as it is driven by anterior …

Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell

Theses and Dissertations

Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the …

Characterization Of Pth Type-2 Receptor ( Pth2rb ) And Its Endogenous Ligand Pth2 In Zebrafish Development, Nicholas Seitz

Theses and Dissertations

Members of the parathyroid hormone family of ligands, PTH (parathyroid hormone), PTH2, and PTHLH (parathyroid hormone-like hormone). These hormones interact with the class B GCPRs parathyroid hormone receptors PTH1R, PTH2R, and PTH3R to regulate a variety of biological processes. In mammals, PTH and PTHLH activate PTH1R and PTH3R to mediate serum calcium homeostasis, chondrogenesis, and bone maintenance. PTH2R activation by PTH2 has been studied primarily in regard to its neuroendocrine roles but is also found in the skin where it contributes to wound healing and keratinocyte differentiation. Still, little is known about the impacts of PTH2R signaling relative to PTH1R …