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Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander May 2024

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H2O2 (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …


Screen For Beneficial Genetic And Chemical Modifiers In Drosophila Models Of Als And Traumatic Brain Injury, Will Bonderer May 2024

Screen For Beneficial Genetic And Chemical Modifiers In Drosophila Models Of Als And Traumatic Brain Injury, Will Bonderer

Biological Sciences Theses and Dissertations

The underlying molecular processes of aberrant protein expression in neurodegeneration are intricate and multifaceted, with ribosome-associated quality control (RQC) emerging as a promising avenue of exploration. Ribosome-associated quality control is integral to cellular function. Its evolutionarily conserved pathway encompasses a network of mechanisms designed to ensure the fidelity of protein synthesis, folding, and degradation within the cells of all eukaryotes. The ribosome, central to protein synthesis, plays a pivotal role in this quality control network, and its malfunction can lead to the accumulation of misfolded or aberrant proteins. In the context of neurodegenerative disorders, this dysfunction can have dire consequences. …


The Development Of Immunohistochemistry (Icc) And Transcriptomic Protocols To Uncover Neurophysiological Markers Of Stress In Red-Eyed Tree Frogs As A Novel Biome, Shirin Dadina May 2024

The Development Of Immunohistochemistry (Icc) And Transcriptomic Protocols To Uncover Neurophysiological Markers Of Stress In Red-Eyed Tree Frogs As A Novel Biome, Shirin Dadina

Senior Theses and Projects

Adverse childhood experiences (ACEs) include various forms of physical and emotional abuse that lead to detrimental long term effects. Agalychnis callidryas (red-eyed tree frogs) have been identified as a novel biomedical model for ACEs. Red-eyed tree frogs demonstrate an escape hatch mechanism under stressors including those from predators, flooding and hypoxia where the embryo undergoes an accelerated developmental process similar to what is observed in the human population regarding precocious puberty. In order to assess this model for neurobiological outcomes of ACEs, morphological and genomic protocols must be developed and validated which is this study’s focus. Paraffin embedding and microtome …


Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis May 2024

Isolation Of Aged Mouse Primary Microglia As A Model System For Alzheimer’S Disease Research, Michael Landis

Biology Honors Papers

Microglia and their role as the immune cells of the central nervous system are an emerging area of interest within Alzheimer’s research, particularly as they have shown in a benevolent and malevolent cellular context. Models of Alzheimer’s disease are very light in studying microglia, so in this study a model of microglia isolated from aged mice is established in order to study the phagocytic activity and protein expression of microglia in response to Amyloid Beta. The cells were isolated from aged mice and cultured before being used to confirm cellular identity, as well as to measure phagocytic activity. This study …


Towards Understanding The Function Of An Ets-Like Gene In Nematostella Vectensis: Generation Of A Knockout Mutant Line And A Transgenic Reporter Line, Emily Bullock May 2024

Towards Understanding The Function Of An Ets-Like Gene In Nematostella Vectensis: Generation Of A Knockout Mutant Line And A Transgenic Reporter Line, Emily Bullock

Biological Sciences Undergraduate Honors Theses

Due to their unique phylogenic position as sister to Bilateria, Cnidaria are often credited with the utility of allowing for reconstruction of ancestral biology based on characteristics shared with bilaterians and other animals. This factor makes investigation into the nervous systems of cnidarians critical in understanding early neural evolution. Wamides, a class of neuropeptides, have been shown to play a regulatory role in life cycle transitions across many different species. The cnidarian specific Wamide neuropeptide, GLWamide, has previously been identified to play an accelerator role in the metamorphic timing of a specific species of sea anemone, Nematostella vectensis. However, …


Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed May 2024

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations & Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …


Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah May 2024

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …


Atlas-Based Analysis Of The Neural Projections From The Lateral Hypothalamic Area To The Lower Brainstem In The Adult Male Rat, Jessica Valeria Salcido Padilla May 2024

Atlas-Based Analysis Of The Neural Projections From The Lateral Hypothalamic Area To The Lower Brainstem In The Adult Male Rat, Jessica Valeria Salcido Padilla

Open Access Theses & Dissertations

Within the last decade, the number of diseases associated with dysregulation of the neural circuits responsible for energy balance, glucosensing, and feeding control has increased. One brain region containing these circuits is the lateral hypothalamic area (LHA), which plays an important role in the sleep/wake cycle, energy balance, and motivated behavior. Although the LHA has been termed a â??feeding centerâ??, other regions within the hindbrain are known for the regulation of similar functions including energy balance, glucosensing, and feeding control. While many studies have explored and reported projections from the LHA to the hindbrain, few have further investigated the interconnections …


Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto Feb 2024

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …


Physically, Mentally, And Emotionally Drained, Kaitlin Medina Jan 2024

Physically, Mentally, And Emotionally Drained, Kaitlin Medina

Regis University Student Publications (comprehensive collection)

Hormonal cycles play an essential role in the development and maturation of young boys and girls into men and women. As teenagers enter their late teens and early twenties, their hormonal cycles are primarily responsible for functions related to fertility and hormone production. During this period of time, these men and women are often in their collegiate years. Overall, the college experience is enjoyable for many students, but it can also be a very stressful time due to a difficult class load and the students’ need to balance their academic, social, and personal lives. Recent studies have analyzed the effects …


The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson Jan 2024

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …


Modulation Of The Crustacean Cardiac Neuromuscular System By The Sly Neuropeptide Family, Grant Griesman Jan 2024

Modulation Of The Crustacean Cardiac Neuromuscular System By The Sly Neuropeptide Family, Grant Griesman

Honors Projects

Central pattern generators (CPGs) are neuronal networks that produce rhythmic motor output in the absence of sensory stimuli. Invertebrate CPGs are valuable models of neural circuit dynamics and neuromodulation because they continue to generate fictive activity in vitro. For example, the cardiac ganglion (CG) of the Jonah crab (Cancer borealis) and American lobster (Homarus americanus) contains nine electrochemically coupled neurons that fire bursts of action potentials to trigger a heartbeat. The CG is modulated by neuropeptides, amines, small molecule transmitters, gases, and mechanosensory feedback pathways that enable flexibility and constrain output. One such modulator, the …


The Role Of Semaphorins In Response To Injury In C. Elegans Neurons, Maria Belen Harreguy Alfonso Dec 2023

The Role Of Semaphorins In Response To Injury In C. Elegans Neurons, Maria Belen Harreguy Alfonso

Dissertations

When neural tissue is injured by trauma, delicate neuronal processes such as axons and dendrites are prone to lesion damage and often disconnect. The molecular, cellular, and circuit mechanisms that underlie the regrowth and reconnection of these processes and the recovery of behavior are major challenges in the fields of neuroscience, regeneration, and resilience. At the molecular and cellular levels, signaling pathways that mediate neuronal growth cone guidance during development can play a role in neuronal regeneration and recovery from injury. One family of signaling proteins involved in this process comprises the highly conserved semaphorins and their receptors, the plexins. …


The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva Aug 2023

The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva

Theses & Dissertations

Visual acuity (VA) is universally accepted as the gold standard metric for ocular vision and function. Contrast sensitivity (CS), color vision, and electrophysiological testing for clinical and occupational settings are warranted despite being deemed ancillary and minimally utilized by clinicians. These assessments provide essential information to subjectively and objectively quantify and obtain optimal functional vision. They are useful for baseline data and monitoring hereditary and progressive ocular conditions and cognitive function. The studies in this dissertation highlight the value of contrast sensitivity, color vision, and cone specific electrophysiological testing, as well as the novel metrics obtained with potential practical clinical …


Sleep Duration Is Associated With Caudate Volume And Executive Function, Nicole Jones May 2023

Sleep Duration Is Associated With Caudate Volume And Executive Function, Nicole Jones

Honors Theses

The ineligible role of the caudate nucleus in sleep has been implicated throughout multiple scientific studies. Previous literature has shown that greater caudate volume is associated with longer habitual sleep duration in older adults- ranging from 55 years of age and up. However, the association between sleep duration and caudate volume remains unknown in the younger population. In this study, we examined the caudate volume in youth to older adults (10 to 85 years old) with a greater sample size (N=464) to increase statistical power. The volumetric size of the caudate nucleus showed significantly positive association with habitual sleep duration, …


Neural Correlates Of Sub-Clinical Grandiose Cluster B Personality Disorders, Adriana Lavarco May 2023

Neural Correlates Of Sub-Clinical Grandiose Cluster B Personality Disorders, Adriana Lavarco

Theses, Dissertations and Culminating Projects

The Cluster B personality disorders (PDs) include antisocial personality disorder (ASPD), borderline personality disorder (BPD), narcissistic personality disorder (NPD), and histrionic personality disorder (HPD). With impulsivity being a commonly shared symptom across the cluster B personality disorders, specifically in BPD, the right and left dorsolateral prefrontal cortex (DLPFC) was targeted for TMS. Since these personality disorders are grouped together due to their shared ‘dramatic’ characteristics, the current study aimed to investigate the effects of transcranial magnetic stimulation (TMS) on the presence of cluster B personality disorder traits in 13 healthy participants. We found that there is a significant decrease in …


Social Exclusion : How Inhibition And Excitation Of The Dorsal Lateral Prefrontal Cortex (Dlpfc) Influences Feelings Of Social Exclusion, Anthony Minervini May 2023

Social Exclusion : How Inhibition And Excitation Of The Dorsal Lateral Prefrontal Cortex (Dlpfc) Influences Feelings Of Social Exclusion, Anthony Minervini

Theses, Dissertations and Culminating Projects

Social exclusion refers to the experience of rejection by one or more people during a social event. Cyberball, a computer program, is one of the most common tools for analyzing social exclusion. Cyberball simulates a game of catch in which any number of individuals or computer- generated players can pass a virtual ball to one another. Regions of the brain that underlies pain perception include networks lined to the Dorsal Lateral Prefrontal Cortex (DLPFC). Direct manipulation of this area may provide a better understanding of how the DLPFC can influence the perception of social exclusion. Transcranial magnetic stimulation (TMS) was …


Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik Apr 2023

Understanding The Expression And Role Of Pros-1 In The Male Gonad Of C. Elegans, Jack Bozik

Undergraduate Theses

The gene pros-1 is a transcription factor that is highly expressed within neuronal sheath cells, glial cells, and excretory canal cells. pros-1 plays a role in cell determination of those cell types in the nematode C. elegans, which promotes organismal development. But the degree to which pros-1 presence is important is still not fully understood, because there are many genes involved in development that when mutated or damaged can result in unexpected phenotypes or even total loss of function to a certain developmental mechanism. What makes pros-1 valuable to research is that it is a functional homologue to a …


Neurogenetic Function Of Host Cell Factor-1, Victoria Lynn Castro Apr 2023

Neurogenetic Function Of Host Cell Factor-1, Victoria Lynn Castro

Open Access Theses & Dissertations

Neural precursor cells (NPCs) are the stem-like cells of the developing brain. These cells differentiate into the differentiated cell types of the central nervous system. If disruption occurs in the number of total NPCs formed or their survival, various disorders including learning disabilities, behavioral problems, or epilepsy can occur. This dissertation describes how the HCFC1 gene controls the proliferation and differentiation of NPCs. HCFC1 encodes for a transcriptional co-factor that regulates the growth and metabolism of stem cells, including NPCs. Mutations in HCFC1 cause cblX syndrome, a neural developmental disorder that affects the nervous system and causes microcephaly, epilepsy, and …


The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King Jan 2023

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …


The Role Of Neurotrophin Signaling In Urinary Bladder Dysfunction With Cyclophosphamide-Induced Cystitis, Harrison Wood Hsiang Jan 2023

The Role Of Neurotrophin Signaling In Urinary Bladder Dysfunction With Cyclophosphamide-Induced Cystitis, Harrison Wood Hsiang

Graduate College Dissertations and Theses

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory pelvic pain syndrome characterized by urinary frequency and urgency, bladder discomfort, decreased bladder capacity, and pelvic pain. A positive feedback loop of bladder inflammation and afferent hypersensitization is currently thought to underlie IC/BPS. Inflammation increases bladder afferent excitability, which in turn releases inflammatory neuropeptides, growth factors, cytokines, and chemokines throughout the micturition pathway, leading to altered bladder function and sensation. There currently exists no effective therapy for IC/BPS.

While its etiology remains unknown, a large body of evidence suggests a role for changes in neurotrophin signaling, particularly that of nerve growth …


Oral Contraceptives And Affective Disorders: Neurobiology And Informed Choice, Sophia Mae Drezner Jan 2023

Oral Contraceptives And Affective Disorders: Neurobiology And Informed Choice, Sophia Mae Drezner

Scripps Senior Theses

Pregnancy prevention and female reproductive freedom have been some of the most contested political issues for decades. Abortion, a fundamental part of women’s healthcare, divides liberals and conservatives on an international scale. The consequences of unintended pregnancy without safe and reliable contraception are widespread, disproportionately impacting women of color, trans and non-binary folks, and poorer communities. The birth control pill is the most common form of oral contraception (OC) globally. Many people with ovaries begin the pill or other hormonal contraceptive (HC) methods as young as 11 years old. Exogenous progesterone and estrogen are known to impact mood, affect, physiology, …


Investigating Neuroanatomical Evolution Through Proliferative Cells In The Astyanax Mexicanus, Sophie Staeger Jan 2023

Investigating Neuroanatomical Evolution Through Proliferative Cells In The Astyanax Mexicanus, Sophie Staeger

Pitzer Senior Theses

The Astyanax mexicanus is a single species of fish that has two very distinct morphs, the cave fish and the surface fish. 200,000 years ago, cave fish ancestors entered the dark and challenging cave environment of Mexico and were forced to adapt in order to survive. Such adaptions include larger fat reserves, more sensitive olfaction, increased neuromasts, and a unique nervous system structure. Yet, other functions regressed, as they lost their eyes and pigmentation. The Duboué lab has established a clear reciprocal relationship between the volume of structures involved in the neuronal adaptations, but the biological mechanisms underlying the development …


The Role Of Serca In Neural Development And Brain Tumors, Hannah M. Christman Jan 2023

The Role Of Serca In Neural Development And Brain Tumors, Hannah M. Christman

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Ion channels are essential for neural function, playing a variety of necessary cellular roles including excitability, maintaining ion gradients, and volume control. While the role of ion channels in neurons is well-defined, much less is known about excitability in neural progenitor cells. Recently it has emerged that these neural precursors may be affected by channelopathies, indicating a critical role of ion channels in neural development. Using the model system Drosophila melanogaster (fruit fly), I investigated the role of the ion channel SERCA (sarco/endoplasmic reticulum Ca2+ATPase). SERCA is a vital calcium ion pump located on the wall of the endoplasmic reticulum, …


Exploring The Molecular Basis Of Touch: A Comparative Analysis Of Gene Expression In Sensory Corpuscle-Rich And Corpuscle-Poor Skin Regions In The Duck, Thomas Hart Jan 2023

Exploring The Molecular Basis Of Touch: A Comparative Analysis Of Gene Expression In Sensory Corpuscle-Rich And Corpuscle-Poor Skin Regions In The Duck, Thomas Hart

Theses and Dissertations--Biology

Cutaneous touch is facilitated by discrete cellular complexes composed of non-neuronal cells associated with mechanoreceptor neuron endings. The non-neuronal cells of these cutaneous end organ complexes (CEOCs) are believed to contribute to touch, but their role in touch sensation remains unclear. To better understand the function of CEOC cells, we sought to characterize the transcriptional profile of CEOC-rich tissue and identify genes expressed in CEOC cells. Bill skin of the tactile foraging Pekin duck (Anas platyrhynchos) is dense with CEOCs, specifically the avian analogs of mammalian Pacinian and Meissner corpuscles, while corpuscles in duck foot skin are scarce. Using RNA …


Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White Jan 2023

Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White

Theses and Dissertations

Notable progress has been made in understanding the development of the neural crest (NC). Neural crest cells (NCCs) can be divided into 4-5 subpopulations. A major lineage among trunk NC derivatives are sympathoadrenal (SA) cells, which give rise to the sympathetic nervous system (SNS). Trunk NCCs follow a ventromedial migration pathway where signals derived from the dorsal aorta instruct migrating NCCs to a SA cell fate. Defects in NC development can result in syndromes known as neurocristopathies. Neuroblastoma is one of the most common forms of pediatric cancer affecting nearly 800 infants each year in the United States (Takita et …


Sense And Sensitivity: Spatial Structure Of Conspecific Signals During Social Interaction, Keshav Ramachandra Jan 2023

Sense And Sensitivity: Spatial Structure Of Conspecific Signals During Social Interaction, Keshav Ramachandra

Graduate Theses, Dissertations, and Problem Reports

Organisms rely on sensory systems to gather information about their environment. Localizing the source of a signal is key in guiding the behavior of the animal successfully. Localization mechanisms must cope with the challenges of representing the spatial information of weak, noisy signals. In this dissertation, I investigate the spatial dynamics of natural stimuli and explore how the electrosensory system of weakly electric fish encodes these realistic spatial signals. To do so In Chapter 2, I develop a model that examines the strength of the signal as it reaches the sensory array and simulates the responses of the receptors. The …


Spatial Processing Of Conspecific Signals In Weakly Electric Fish: From Sensory Image To Neural Population Coding, Oak Everette Milam Jan 2023

Spatial Processing Of Conspecific Signals In Weakly Electric Fish: From Sensory Image To Neural Population Coding, Oak Everette Milam

Graduate Theses, Dissertations, and Problem Reports

In this dissertation, I examine how an animal’s nervous system encodes spatially realistic conspecific signals in their environment and how the encoding mechanisms support behavioral sensitivity. I begin by modeling changes in the electrosensory signals exchanged by weakly electric fish in a social context. During this behavior, I estimate how the spatial structure of conspecific stimuli influences sensory responses at the electroreceptive periphery. I then quantify how space is represented in the hindbrain, specifically in the primary sensory area called the electrosensory lateral line lobe. I show that behavioral sensitivity is influenced by the heterogeneous properties of the pyramidal cell …


Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury Dec 2022

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …


Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar Dec 2022

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations & Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …