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Theses and Dissertations

Molecular Biology

Zebrafish

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Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt Jan 2018

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 …


Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu May 2015

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 Jan 2015

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 …


Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh Dec 2014

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 …


The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki Dec 2013

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 …