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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 …

Determining The Effects Of Mistranslating Transfer Rna Variants On Drosophila Melanogaster, Joshua R. Isaacson

Electronic Thesis and Dissertation Repository

Transfer RNAs (tRNAs) play a central role in translation as adaptor molecules between mRNA and protein. Variant tRNAs can cause the misincorporation of an amino acid into a growing polypeptide. Mistranslating tRNA variants are surprisingly common in humans but the effects of mistranslating tRNA variants on eukaryotic biology are poorly understood. My thesis aimed to create a model of tRNA-induced mistranslation using the fruit fly Drosophila melanogaster and characterize the effects of mistranslating tRNA variants on eukaryotic biology.

I first integrated a gene encoding a serine tRNA variant that induced proline-to-serine (P>S) mistranslation into the fly genome. Proteins isolated …

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 …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Incorporating A Developmental Perspective Into Gene Identification Models For Alcohol Use Behaviors, Nathaniel S. Thomas

Theses and Dissertations

Frequent alcohol use can lead to alcohol use disorder, which accounts for three million deaths and over 133 million life years lost to disability and death worldwide per year. Alcohol use behaviors unfold across development, beginning with initiation of drinking and progressing through various escalating stages of use. Alcohol use behaviors are also under genetic influence. Genome-wide association represents the state-of-the-science statistical methodology for identifying genes associated with alcohol use outcomes. However, contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. In this project, I applied novel multivariate genomic methods to combine …

Characterizing The Expression Pattern And Function Of Tartan During Drosophila Development, Alaina Baggett

Biomedical Engineering Undergraduate Honors Theses

The development of complex structures and organs by multicellular organisms relies on the ability of epithelial cells to self-organize. Epithelia are sheets of connected cells, and compartment boundaries are formed between certain epithelial cells to create distinct tissue compartments. Compartment boundaries are specialized cell-cell interfaces that are enriched for the cytoskeletal proteins actin and myosin, leading to straight cell edges under relatively high tension that act as fences keep cells from moving between compartments. In the model organism Drosophila melanogaster (fruit fly), compartment boundaries in the early embryo are established in response to the non-uniform striped expression of the cell-surface …

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 Origins & Functional Effects Of Postzygotic Mutations Throughout The Human Lifespan, Nicole Briana Rockweiler

Arts & Sciences Electronic Theses and Dissertations

Mosaicism is pervasive in humans and yet we understand little of its causes and functional consequences across the lifespan. To help solve these mysteries, we developed a suite of tools, called Lachesis, to analyze postzygotic mutations (PZMs). LachesisDetect is a novel and accurate method to detect PZMs with VAFs as low as 0.04% from bulk RNA-seq samples. LachesisMap is an innovative supervised method to reconstruct postzygotic mutation phylogenies from putative prenatal PZMs. We applied Lachesis to 17,382 samples derived from 948 donors across 54 diverse tissues and cell types from the NIH’s Genotype-Tissue Expression (GTEx) project to produce the most …

Developmental Regression Analysis And Investigation Of Genotype Correlations In Individuals With Classic Rett Syndrome, Aubrey Lynn Rose

Theses and Dissertations

Rett syndrome (RTT) is a neurodevelopmental disorder impacting 1 in 10,000 females worldwide, making it one of the most common causes of complex disability in girls. RTT is caused by pathogenic variants in the MECP2 gene and is characterized by developmental regression, stereotypical hand movements, and an abnormal gait. Despite consistency in the presence of these core features, a wide range of features and varying severity can be observed in girls with RTT. Similarly, the particular type of MECP2 variant present also differs between patients. Previous studies have assessed correlations between genotype and phenotype in patients with RTT. While past …

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 …

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 …

Dietary Development And Nutritional Ontogeny In Gorilla Beringei : A Multi-Layered, -Omics Approach, Emma C. Cancelliere

Dissertations, Theses, and Capstone Projects

In species who consume folivorous diets, immature individuals must contend with the challenges of extracting nutrients from fibrous foods before dietary adaptations and strategies are fully developed. Additionally, immatures have distinct nutritional needs to support their stage-specific metabolic and biophysiological requirements. To meet these stage-specific needs, while constrained by underdeveloped feeding strategies and digestive capacities, immatures may adopt distinct diets better suited to their specific developmental context. However, where dietary modification is constrained by low dietary diversity or landscape homogeneity, it is unclear how immature individuals compensate through alternative strategies. In turn, little is known about the nutritional and life …

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 …

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 …

Investigation Into The Roles Of Her9 And Capn5 During Retinal Development And Regeneration, Cagney Coomer

Theses and Dissertations--Biology

The formation of a healthy and functioning eye requires coordinated interactions between numerous signaling pathways and gene regulatory networks within the developing neural retina. Tight regulation of gene expression is required for cell specification and differentiation in this multilayered, light sensitive tissue. The photoreceptors are the light detecting cells of the retina, capable of functioning in both intense sunlight and dim light at night. When pigment cells of the photoreceptor outer segment are activated by light, a complex chain of events called phototransduction leads to the electrical signal cascade that is transmitted through the retina and ultimately to the brain …

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 …

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 …

Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine

Arts & Sciences Electronic Theses and Dissertations

Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …

Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura

Graduate Theses, Dissertations, and Problem Reports

Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …

The Role Of T-Box Proteins In Vertebrate Germ Layer Formation And Patterning, Sushma Teegala

Dissertations, Theses, and Capstone Projects

All of the tissues in triploblastic organisms, with the exception of the germ cells, arise from the three germ layers, ectoderm, mesoderm and the endoderm. The identification of the genes that underlie the differentiation of these layers is crucial to our understanding of development. T-box family proteins are DNA-binding transcriptional regulators that play important roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in …

Applying The Water Governance Framework On Rural Water Development Projects In Guatemala, Muhanad M. Alkharaz

Theses and Dissertations

According to the Organization for Economic Cooperation and Development (OECD), ‘Water crisis is mainly a governance crisis’, (OECD, 2013). Many water experts, as individuals, organizations and even governmental bodies have developed water governance frameworks to overcome water challenges on local, national, and international levels such as Integrated Water Resource Management. In rural areas, especially in developing countries, access to safe drinking water is a daily challenge due to a variety of political, economic, and social constraints. For in-stance, some developing countries have a strong centralized governance system. Due to lack of capacity and resources, central governments are incapable of providing …

Evolvability Of The Skull: A Study Of Genetic Basis And Integration In The Teleost Craniofacial Skeleton, Yinan Hu

Doctoral Dissertations

As the field of evolutionary biology pivots away from a gene-centric view of how adaptive evolution proceeds, renewed emphasis is placed on the origin of phenotypic variation. Understanding the developmental processes that underlie the production of novel traits, and how they might influence evolvability, is considered a primary goal in the on-going “extended evolutionary synthesis”. The following dissertation explores these questions in the context of adaptive radiations in fish, with a focus on morphological variation in the craniofacial skeleton. Specifically, the first chapter investigates the genetic and developmental basis of shape (co-)variation in the feeding apparatus of African cichlid fishes, …

Characterization Of Somatically-Eliminated Genes During Development Of The Sea Lamprey (Petromyzon Marinus), Stephanie A. Bryant

Theses and Dissertations--Biology

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during early development that facilitate the elimination of ~20% of the genome from the somatic cell lineage, resulting in distinct somatic and germline genomes. To improve our understanding of the evolutionary/developmental logic of PGR, we generated computational predictions to identify candidate germline-specific genes within a transcriptomic dataset derived from adult germline and the embryonic stages encompassing PGR. Validation studies identified 44 germline-specific genes and characterized patterns of transcription and DNA loss during early embryogenesis. Expression analyses reveal that several of these genes are differentially expressed during early embryogenesis …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

In Vivo Significance Of The Mdm4 And P73 Interaction During Development And Tumorigenesis, Mehrnoosh Tashakori

Dissertations & Theses (Open Access)

The tumor suppressor protein p53 is negatively regulated by Mdm4 protein. The significance of such regulation was determined from mouse models. Mdm4-deficient mice are embryonic lethal at E7.5 in a p53-dependent manner. p73, a member of the p53-family, is a transcription factor with tumor suppressor activity. In vitro studies show that Mdm4 binds to p73 and, further, comprehensive biochemical studies revealed that Mdm4 has higher affinity for p73 than p53. However, little is known about the significance of the Mdm4 and p73 interaction in vivo. This study aimed to elucidate the biological consequences of this interaction during embryogenesis …

Developing A Gene Editing System To Study Haplodiploidy In The Jewel Wasp, Nasonia Vitripennis, Emily A. Muller

Scripps Senior Theses

Hymenopteran insects, which include all ants, bees and wasps, reproduce through a poorly understood form of reproduction known as haplodiploidy. A promising experimental system for understanding this developmental process is the jewel wasp, Nasonia vitripennis. A critical aspect of using Nasonia as a model is establishing an effective means for editing specific genes of interest so that their functions can be studied through genetic means. For my thesis research, I performed a pilot study of the gene editing method known as CRISPR in Nasonia. I targeted the single heterochromatin protein 1 (HP1) gene present in the Nasonia genome …

Phylogeny And Population Genetics Of The Endangered Dwarf Bear-Poppy, Arctomecon Humilis Coville (Papaveraceae) Using Microsatellite Markers, Joshua Simpson

Dissertations, Theses, and Capstone Projects

The genus Arctomecon (Papaveraceae) is comprised of three narrowly endemic rare species that are largely restricted to gypsum soils of the eastern Mojave Desert. The small, remaining populations of these species have become increasingly isolated by urban development and habitat fragmentation. Arctomecon humilis is federally listed as endangered due to its limited distribution within a ~15 km radius of an actively expanding city. Organizations involved with land management and conservation have called for greater insight into the genetic variation and population structure of the remaining subpopulations as they make important decisions regarding where to focus their efforts and resources.

The …

Translational Regulation In Arabidopsis Thaliana: Genetic And Functional Characterization Of Eukaryotic Initiation Factor 3, Bijoyita Roy

Doctoral Dissertations

Molecular functions of eukaryotic initiation factor 3 (eIF3) in translation are manifold, encompassing events from initiation complex assembly to translation termination. The contribution of the individual subunits of eIF3 to its multiple activities is quite unclear. It has been hypothesized that several of its 13 subunits contribute to mRNA specific regulation. Prior research had established that the h subunit of eIF3 in Arabidopsis was required for translation of specific mRNAs as well as for organ formation and meristem development. This study aims towards understanding the functions of individual subunits of eIF3 in the context of plant development and to further …

Phenotypic Plasticity And The Post-Modern Synthesis: Integrating Evo-Devo And Quantitative Genetics In Theoretical And Empirical Studies, Alison G. Scoville

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Mainstream evolutionary biology lacks a mature theory of phenotype. Following from the Modern Synthesis, researchers tend to assume an unrealistically simple mapping of genotype to phenotype, or else trust that the complexities of developmental architecture can be adequately captured by measuring trait variances and covariances. In contrast, the growing field of evolutionary developmental biology (evo-devo) explicitly examines the relationship between developmental architecture and evolutionary change, but lacks a rigorous quantitative and predictive framework. In my dissertation, I strive to integrate quantitative genetics and evo-devo, using both theoretical and empirical studies of plasticity. My first paper explores the effect of realistic …