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The Role Of The Basement Membrane In Basal Tissue Folding, Elizabeth Falat
The Role Of The Basement Membrane In Basal Tissue Folding, Elizabeth Falat
Theses and Dissertations
The ability of organs and tissues to function properly is reliant on the correct formation of shape. Proper morphogenesis is carefully regulated by both intracellular dynamics and extracellular mechanical forces. Using the highly conserved zebrafish midbrain-hindbrain boundary (MHB), we investigated the role of the basement membrane, a specialized extracellular matrix that basally lines the tissue, in mediating cell shapes and mechanical tissue stresses during basal tissue folding. A primary component of the basement membrane is laminin-111, a heterotrimer composed of the alpha1, beta1 and gamma1 chains, encoded by lama1, lamb1a, and lamc1 genes respectively. We investigated the role of each …
Assessing The Effects Of Levonorgestrel (Lng) On Neural Differentiation In The Developing Hypothalamus Using The Zebrafish (Danio Rerio) As A Model, Gabriella Hinojosa
Assessing The Effects Of Levonorgestrel (Lng) On Neural Differentiation In The Developing Hypothalamus Using The Zebrafish (Danio Rerio) As A Model, Gabriella Hinojosa
Theses and Dissertations
Neurogenesis is a critical component of fetal neurodevelopment consisting of: migration, proliferation and differentiation. Health concerns from anxiety to reproductive issues have been linked to alterations of neurogenesis processes. Endocrine disrupting chemicals (EDCs) can mimic hormones vital to this process, potentially adversely affecting the susceptible fetal brain. One EDC, Levonorgestrel (LNG), is a testosterone-like progestin used in birth control methods that has a high bioavailability and long half-life. Using zebrafish embryos as a model, this lab previously discovered that an environmentally relevant LNG dose (5 ng/L) significantly increased anxiety behaviors. The hypothalamus is responsible for the development …
Governing Dynamics Of Divalent Copper Binding By Influenza A Matrix Protein 2 His37 Imidazole, Kelly Lewis Mcguire
Governing Dynamics Of Divalent Copper Binding By Influenza A Matrix Protein 2 His37 Imidazole, Kelly Lewis Mcguire
Theses and Dissertations
Influenza A is involved in hundreds of thousands of deaths globally every year resulting from viral infection-related complications. Previous efforts to subdue the virus by preventing proper function of wild-type (WT) neuraminidase (N), and M2 proteins using oseltamivir and amantadine (AMT) or rimantadine (RMT), respectively, exhibited success initially. Over time, these drugs began exhibiting mixed success as the virus developed drug resistance. M2 is a proton channel responsible for the acidification of the viral interior which facilitates release of the viral RNA into the host. M2 has a His37-tetrad that is the selective filter for protons. This protein has been …
Embryonic Exposure To The Synthetic-Progesterone Levonorgestrel (Lng) Results In Hyperactive Behavior In Zebrafish (Danio Rerio), Austin D. Fuentes
Embryonic Exposure To The Synthetic-Progesterone Levonorgestrel (Lng) Results In Hyperactive Behavior In Zebrafish (Danio Rerio), Austin D. Fuentes
Theses and Dissertations
Exposure to endocrine-disrupting chemicals has been associated with an increased risk of anxiety-like behavior at various life stages. Levonorgestrel (LNG), a synthetic contraceptive, could potentially alter steroidal regulated brain development based on the findings of this thesis. In-silico measurements were used for comparing LNG, which had been found in surface water, to chemical databases to predict the bioavailability, half-life, and estrogen binding potential. Zebrafish (Danio rerio) for illuminating the effects of LNG exposure during early zebrafish embryonic development, similar to fetal development, on behavior was investigated. Our data suggests exposure in a dose-dependent manner of LNG can potentially …
The Role Of Ca2+/Calmodulin Dependent Protein Kinase Ii, Camk-Ii, In Kidney Morphogenesis, Sarah R. Ingram
The Role Of Ca2+/Calmodulin Dependent Protein Kinase Ii, Camk-Ii, In Kidney Morphogenesis, Sarah R. Ingram
Theses and Dissertations
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common heritable diseases in the world, characterized by the development of large fluid filled cyst. Treatments for this disease are limited due to a lack of understanding of disease pathogenesis. Ca2+/calmodulin dependent protein kinase II (CaMK-II) is necessary for kidney morphogenesis in zebrafish as well as being a downstream effector of pkd2, one of the genes most commonly mutated in ADPKD patients. The roles of CaMK-II during zebrafish kidney development include regulation of kidney cell migration as well as cloacal cilia stability. The influence of CaMK-II …
An Assessment Of Bsa Protein Hydrogel Biocompatibility In The Vertebrate Intestinal Tract, Ryan Joseph Garde
An Assessment Of Bsa Protein Hydrogel Biocompatibility In The Vertebrate Intestinal Tract, Ryan Joseph Garde
Theses and Dissertations
The fields of biomedicine and pharmacology have a mission to design methods to treat disease while minimizing adverse side effects using novel drug delivery systems. In developing new therapeutic systems, it is crucial to test that drug delivery systems target pathological cells and tissue and is non-toxic in healthy tissue. One promising method for targeted drug delivery is the use of hydrogels as carriers. Here, we studied the effects of bovine serum albumin (BSA) hydrogel consumption to assess the potential for hydrogel use in treating intestinal disease via oral administration. We investigated intestinal architecture and cell populations following hydrogel treatments …
A Crispr/Cas9 Tissue Specific Forward Genetic Screening Method In Danio Rerio, Joshua Don Yates
A Crispr/Cas9 Tissue Specific Forward Genetic Screening Method In Danio Rerio, Joshua Don Yates
Theses and Dissertations
Many of the cutting-edge innovations on the CRISPR/Cas9 system involve the use of complex sgRNA libraries. For example, such libraries have recently been used in functional genomics applications to screen for specific genes in both cell lines and living organisms, as well as in subcellular imaging to fluorescently label chromatin in living cells. However, chemically synthesizing customized libraries can be cost prohibitive, requires precise genomic information, and can takes several weeks. We developed a rapid and efficient enzymatic method to generate sgRNA libraries from arbitrary DNA substrates, significantly reducing the cost of library generation. A type IIS restriction enzyme binding …
Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt
Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt
Theses and Dissertations
Acute myeloid leukemia (AML) is the second most common type of leukemia and accounts for 80% of adult acute leukemia cases and is characterized by the accumulation of poorly or undifferentiated myeloid blast cells. Standard treatment includes chemotherapy, which if unsuccessful, is followed by more rigorous chemotherapy as well as stem cell transplantation. Considering most patients are over the age of 45, these more rigorous therapies are not always possible, and as such, new therapies must be developed. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) that results in the expression of an MLL fusion protein …
Ca2+/Calmodulin-Dependent Protein Kinase Type Ii (Camk-Ii) Is Required For Hematopoietic Stem Cell Specification, Camden E. Kurtz
Ca2+/Calmodulin-Dependent Protein Kinase Type Ii (Camk-Ii) Is Required For Hematopoietic Stem Cell Specification, Camden E. Kurtz
Theses and Dissertations
Ca2+/Calmodulin-dependent protein kinase type II (CaMK-II) is a Serine/Threonine protein kinase that is activated by Ca2+ and Calmodulin to phosphorylate substrates involved in myriad developmental processes. This project implicates CaMK-II in specification of HSCs, and zebrafish provide an ideal embryonic model to study hematopoiesis. Zebrafish genetic manipulation was achieved through: incubation in chemical inhibitors; injection of notochord-targed WT and DN CaMK-II constructs with Transposase; and injection of camk2g1 translation-blocking morpholino antisense oligonucleotide (MO). Whole-mount in situ hybridization (WISH) and immunolocalization on zebrafish embryos allowed visualization of key HSC markers and pathway components that implicated CaMK-II in the specification of HSCs. …
Zebrafish (Danio Rerio) As A Model For Orofacial Research, Kevin A. Ghaffari
Zebrafish (Danio Rerio) As A Model For Orofacial Research, Kevin A. Ghaffari
Theses and Dissertations
Across species, the face and more specifically the mouth, serves as an essential facet of everyday life. Amongst humans the mouth serves as a tool for the ingestion of food, a marker for facial recognition and a medium for communication. In order for the mouth to properly form, a series of precise growth and fusion events are needed. In order to insure that these events are orchestrated properly is a wide array of signals, transcription factors and epigenetic regulators. Due to the needed precision of these events, congenital birth defects of the face such as cleft lip and cleft palate …
Effects Of Global Dna Methylation Changes On Neurobehavior In Zebrafish, Matthew Christopher Pickens
Effects Of Global Dna Methylation Changes On Neurobehavior In Zebrafish, Matthew Christopher Pickens
Theses and Dissertations
A number of environmental neurotoxicants modulate DNA methylation, but its influence on neurobehavior remains unclear. The laboratory has established that low-level developmental methylmercury exposure induces neurobehavioral deficits; the current results demonstrate that it also induces global DNA hypomethylation. DNA methyltransferase 1-mutant zebrafish (exhibit ~70% reduction in enzymatic activity) were used to assess the role of DNA hypomethylation on behavior. Several neurobehavioral assays including the C-start escape, circadian rhythm, basic locomotion and visual-motor response (VMR) were also performed. There was a significant difference in VMR between the wild type and mutant animals. Other behavior assays revealed no significant difference, primarily due …
Neurobehavioral And Gene Expression Effects Of Early Embryonic Methylmercury Exposure In Yellow Perch (Perca Flavescens) And Zebrafish (Danio Rerio) Larvae, Francisco Xavier Mora Zamorano
Neurobehavioral And Gene Expression Effects Of Early Embryonic Methylmercury Exposure In Yellow Perch (Perca Flavescens) And Zebrafish (Danio Rerio) Larvae, Francisco Xavier Mora Zamorano
Theses and Dissertations
Methylmercury (MeHg) is a pervasive and persistent neurotoxic environmental pollutant known to affect the behavior of fish, birds and mammals. The present study addresses the neurobehavioral and gene expression effects of MeHg in yellow perch (Perca flavescens) and zebrafish (Danio rerio) embryos. The rationale for this study originated from an interest to understand the behavioral and molecular phenotypes of environmental MeHg exposure in the yellow perch, an ecologically and economically relevant species of the North American Great Lakes region. Both MeHg and the yellow perch coexist in a common ecosystem: the North American Great Lakes. However, the effects of this …
Female Reproductive Impacts Of Dietary Methylmercury In Yellow Perch (Perca Flavescens) And Zebrafish (Danio Rerio), Abigail Rachael Debofsky
Female Reproductive Impacts Of Dietary Methylmercury In Yellow Perch (Perca Flavescens) And Zebrafish (Danio Rerio), Abigail Rachael Debofsky
Theses and Dissertations
This study sought to evaluate the effects of dietary MeHg exposure on female teleost reproduction and phenotypically-anchor gene dysregulation in adult yellow perch (Perca flavescens) and zebrafish (Danio rerio) in order to establish relevant biomarkers relating exposure and subsequent reproductive effects. Yellow perch were used in the study for their socioeconomic importance within the Great Lakes basin, and their significance to the food web. Utilization of zebrafish allowed for a detailed analysis of the molecular effects of MeHg and established its relevance as a model for other fish species. MeHg exposures at environmentally relevant levels were done in zebrafish for …
Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu
Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu
Theses and Dissertations
Elucidating the molecular mechanisms that play a role in cellular morphogenesis is critical to our understanding of brain development and function. The midbrain-hindbrain boundary (MHB) is one of the first folds in the vertebrate embryonic brain and is highly conserved across species. We used the zebrafish MHB as a model for determining the molecular mechanisms that regulate these cell shape changes. Cellular morphogenesis is tightly regulated by signaling pathways that rearrange the cytoskeleton and produce mechanical forces that enable changes in cell and tissue morphology. The generation of force within a cell often depends on motor proteins, particularly non-muscle myosins …
Functional Characterization Of Rai1 In Zebrafish, Joshua S. Beach
Functional Characterization Of Rai1 In Zebrafish, Joshua S. Beach
Theses and Dissertations
Smith-Magenis Syndrome (SMS; OMIM #182290) is a multiple congenital abnormality and intellectual disability (ID) disorder caused by either an interstitial deletion of the 17p11.2 region containing the retinoic acid induced-1 (RAI1) gene or a mutation of the RAI1 gene. Individuals diagnosed with SMS typically present characteristics such as ID, self-injurious behavior, sleep disturbance, ocular and otolaryngological abnormalities, craniofacial and skeletal abnormalities, neurological and behavioral abnormalities, as well as other systemic defects and manifestations. Previous work by Vyas in 2009 showed temporal expression of rai1 in zebrafish embryos as early as 9 hpf. We hypothesize that there is maternal …
A Structure/Function Analysis Of Nhsl1b In Facial Branchiomotor Neurons, John Ojumu
A Structure/Function Analysis Of Nhsl1b In Facial Branchiomotor Neurons, John Ojumu
Theses and Dissertations
The goal of this study was to identify critical regions of a novel gene, Nance-Horan syndrome-like 1b (nhsl1b). It was previously discovered that C-terminal truncation of the Nhsl1b protein in nhsl1b mutants resulted in a loss of migration in the facial motor neurons of the hindbrain (Walsh et al. 2011). As nhsl1b expresses many isoforms, multiple targets were investigated in order to determine which transcript bears the largest impact on the motor neurons. Using confocal microscopy to observe immunostained embryos, we examined a mutation in an nhsl1b transcript that encodes a WHD, a domain that is known to …
Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh
Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh
Theses and Dissertations
Damage to the central nervous system (CNS) circuitry of adult mammals results in permanent disability. In contrast, the ability to regenerate damaged CNS nerves and achieve functional recovery occurs naturally in fish. The ability of fish to successfully regrow damaged CNS nerves is in part a consequence of their ability to re-express key neuronal growth-associated genes/proteins in response to CNS injury. On such protein is Growth-Associated Protein-43 (Gap43), a protein which is highly enriched in axonal growth cones during CNS development and regeneration. Experiments conducted in mammals have demonstrated that ectopic expression of GAP-43 improves axonal re-growth after injury. Using …
Zebrafish As A Model For Determining The Mechanisms Causing Deafness In Myh9-Related Disease, Luke David Spychalla
Zebrafish As A Model For Determining The Mechanisms Causing Deafness In Myh9-Related Disease, Luke David Spychalla
Theses and Dissertations
Approximately 1 in 500 infants are diagnosed with hearing loss, and about half of these cases can be traced to genetic defects. Several hundred genes have been implicated in deafness, including MYH9, which codes for the conventional motor protein non-muscle myosin IIA (NMIIA). Mutations in MYH9 lead to syndromic MYH9-related diseases, which include deafness as a variable symptom, as well as non-syndromic autosomal deafness DFNA17. Despite its identification as a deafness gene, the functions of MYH9 in ear development and hearing remain unknown. To study this role, we will use zebrafish as a model. Zebrafish offer significant advantages including established …
The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki
The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki
Theses and Dissertations
Developing neurons extend processes to specific targets and establish connections that are essential for future function of the nervous system. One of these processes, the axon, has a motile tip called a growth cone that rearranges its membrane-associated actin cytoskeleton to turn toward or away from environmental guidance cues. Growth associated protein 43 (GAP-43) is one of the most abundant proteins associated with axonal growth cone membranes and is known to modulate the formation and stability of the actin cytoskeleton during axon guidance. Protein kinase C (PKC)-mediated phosphorylation of GAP-43 on serine 42 regulates its interactions with actin. Phosphorylated GAP-43 …
Camk-Ii: An Integral Protein In Cell Migration, Jamie Josephine Avila Mcleod
Camk-Ii: An Integral Protein In Cell Migration, Jamie Josephine Avila Mcleod
Theses and Dissertations
Coordinated inductive and morphogenetic processes of gastrulation establish the zebrafish body plan. Gastrulation includes massive cell rearrangements to generate the three germ layers and shape the embryonic body. Three modes of cell migration must occur during vertebrate gastrulation and include: epiboly, internalization of the presumptive mesendoderm and convergent extension (C&E). C&E movements narrow the germ layers mediolaterally (convergence) and elongate them anteroposteriorly (extension) to define the embryonic axis. The molecular mechanisms regulating coordinated cell migrations remain poorly understand and studying these has become of great interest to researchers. Understanding cell migration during development is highly relevant to a number of …
Adverse Outcome Pathways: A Framework For Identifying Chemical Mode Of Action During Zebrafish Embryogenesis, Krystle Yozzo
Adverse Outcome Pathways: A Framework For Identifying Chemical Mode Of Action During Zebrafish Embryogenesis, Krystle Yozzo
Theses and Dissertations
Human health and ecological risk assessors are currently facing increased demands and public pressure to evaluate the potential risk of hundreds to thousands of chemicals based on limited toxicity data. Therefore, scientifically sound models are needed to predict toxicity without sole reliance on conventional whole-organism (vertebrate) bioassays. To help address this challenge, adverse outcome pathways (AOPs) have recently been proposed as conceptual tools to help link direct, molecular-level initiating events to adverse outcomes at higher levels of biological organization. Additionally, using AOPs as frameworks, high-throughput screening (HTS) and high-content screening (HCS) assays have been recently proposed as key components of …
Complexity And Uncertainty In Human And Ecological Risk Assessment, Matthew Jordan Dellinger
Complexity And Uncertainty In Human And Ecological Risk Assessment, Matthew Jordan Dellinger
Theses and Dissertations
Multiple interacting stressors in the environment present increasingly complex risks to human health. Too often, however, the data required for traditional risk assessment are either lacking or unavailable at the necessary spatial or temporal scale. In addition, assessment practices and management policies need to move away from single factor approaches in order to accommodate the reality of complex chemical mixtures and environmental stressors. Recent literature suggests that a paradigm shift is under way. This points to a need for the development of new techniques both for rapid data collection and flexible risk assessment strategies that can adapt to make use …