Cell and Developmental Biology Commons^™

Biochemical And Functional Characterization Of Semaphorin6a-Plexina Signaling In Zebrafish Eye Development, Riley St. Clair

Graduate College Dissertations and Theses

During embryonic development, cells respond to extracellular signals to establish proper tissue organization. Semaphorins (Semas) are a large class of secreted and transmembrane proteins that signal through Plexin (Plxn) receptors to guide migrating cells to their correct position and thus play critical roles in the development of various tissues including the nervous and cardiovascular systems. We have previously shown that Sema6A-PlxnA2 signaling is essential for visual system development, as decreasing endogenous Sema6A or PlxnA2 in zebrafish results in decreased cohesion of the early eye field, impaired retinal lamination, and smaller eye size. However, the molecular mechanisms governing these phenotypes are …

Exosomes And Their Role In Asbestos Exposure And Mesothelioma, Phillip Blake Munson

Graduate College Dissertations and Theses

Malignant mesothelioma (MM) is a locally invasive and highly aggressive cancer arising on the mesothelial surface of organ cavities (mainly pleural) as a direct result of asbestos exposure. The latency period of MM is long (20-50yrs) after initial asbestos exposure, and the prognostic outcomes are dismal with median life expectancy of 6-12 months post-diagnosis. There are no useful biomarkers for early MM diagnosis, no successful therapeutic interventions. These vast voids of knowledge led to our hypotheses that secreted vesicles, termed exosomes, play an important role in MM development and tumorigenic properties. Exosomes are nano-sized particles secreted from all cell types …

Investigation Of Transforming Growth Factor-Alpha And Its Potential Role In Promoting Ovarian Follicular Dominance, Allie Lynn Lundberg

Graduate College Dissertations and Theses

Intraovarian growth factors play a vital role in influencing the fate of ovarian follicles. They affect proliferation versus apoptosis of granulosa cells (GCs), and can influence whether small antral follicles continue their growth or undergo atresia. Transforming Growth Factor-alpha (TGFα), an oocyte-derived growth factor, is thought to regulate granulosa cell function, yet has been largely overshadowed by current interest in TGF-beta superfamily members, such as bone morphogenetic proteins (BMPs) and anti-Mullerian hormone (AMH). In the current study, effects of TGFα on bovine GC proliferation, intracellular signaling and cytokine-induced apoptosis were evaluated. Briefly, all small antral follicles (3-5mm) from bovine ovaries …

Effects Of Tumor-Related Factors And Chemotherapy On Skeletal Muscle And The Protective Effects Of Exercise, Blas Anselmo Guigni

Graduate College Dissertations and Theses

Cancer patients often experience cachexia, a form of weight loss consisting mostly of skeletal muscle wasting. Muscle wasting leads to physical disability, poor quality of life, reduced tolerance to treatments and shorter survival. Although the causes of cancer-related muscle atrophy have been studied for decades, the exact mechanisms through which cancer and its treatments promote muscle wasting have yet to be defined.

The overall aim of this dissertation is to examine the mediators of muscle wasting in cancer patients during their treatment and examine the modulatory role of exercise to maintain muscle size and function. To address these aims, we …

Investigating The Role Of Histidyl-Trna Synthetase In Zebrafish Nervous System Development, Ashley Waldron

Graduate College Dissertations and Theses

Histidyl-tRNA Synthetase (HARS) is a member of the family of enzymes that are responsible for attaching specific amino acids to their corresponding tRNA molecules. This function is critical for accurate and efficient protein synthesis and therefore is required in every cell of an organism. Interestingly, there are a growing number of tissue-specific disorders associated with mutations in genes for this family. For example, mutations in HARS have been associated with three different genetic disorders. The tissue most commonly affected in these disorders is nervous tissue and symptoms range from peripheral neuropathy to severe cognitive impairment. The bias towards nervous system …

Inflammation Of The Taste Sensory System: Cyclophosphamide And Amifostine, Anish Ali Sarkar

Graduate College Dissertations and Theses

Chemotherapeutics are used extensively to treat cancer patients and often induce adverse effects, including taste dysfunctions. Disturbances in taste are detrimental to the overall well-being of cancer patients, causing malnutrition and weight loss that aggravate their condition even further. Inflammation due to an infection of the taste sensory system as previously shown, has detrimental effects on the taste sensation. Our study focused on if chemotherapy induced an inflammatory response in the taste buds using cyclophosphamide (CYP), a pro-drug. Once metabolized by the P450 enzyme complex, its primary metabolite functions as an alkylating agent, involved in inhibiting cell replication cycle and …

Neurodevelopmental Roles Of Semaphorin6a/Plexina2 Signaling In Zebrafish, Sarah Elizabeth Emerson

Graduate College Dissertations and Theses

ABSTRACT

A multitude of complex cellular changes are required throughout development in order for a single cell to transform into a fully functioning organism. Cellular events including proliferation, migration, and differentiation have to be carefully controlled in order for development to proceed correctly. In order to study such dynamic processes, in vivo models are often utilized. Using the zebrafish (Danio rerio) as a model system, we have investigated the role of an axon guidance signaling pair, Semaphorin6A (Sema6A) and PlexinA2 (PlxnA2), in neurodevelopment.

A previous investigation into the developmental expression patterns of sema6A and plxnA2 in zebrafish, revealed overlapping expression …

The Metabotropic Glutamate Receptor Mglur1 Regulates The Voltage-Gated Potassium Channel Kv1.2 Through Agonist-Dependent And Agonist-Independent Mechanisms, Sharath Chandra Madasu

Graduate College Dissertations and Theses

The voltage gated potassium channel Kv1.2 plays a key role in the central nervous system and mutations in Kv1.2 cause neurological disorders such as epilepsies and ataxias. In the cerebellum, regulation of Kv1.2 is coupled to learning and memory. We have previously shown that blocking Kv1.2 by infusing its specific inhibitor tityustoxin-kα (TsTX) into the lobulus simplex of the cerebellum facilitates eyeblink conditioning (EBC) and that EBC itself modulates Kv1.2 surface expression in cerebellar interneurons. The metabotropic glutamate receptor mGluR1 is required for EBC although the molecular mechanisms are not fully understood. Here we show that infusion of the mGluR1 …