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Articles 1 - 30 of 46
Full-Text Articles in Developmental Biology
The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson
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, …
Functional Analysis Of The Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha-1 (Gabra1) Gene During Zebrafish Development., Nayeli Gabriela Reyes-Nava
Functional Analysis Of The Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha-1 (Gabra1) Gene During Zebrafish Development., Nayeli Gabriela Reyes-Nava
Open Access Theses & Dissertations
The GABRA1 gene encodes for the alpha-1 (α1) subunit of the Gamma-Aminobutyric acid type A receptor (GABAAR), which are the primary modulators of synaptic inhibition in the central nervous system (CNS). Alpha-1 subunits are essential for maintaining the normal function of native receptors and contribute to over 60% of all GABAARs in the CNS. Remarkably, a broad spectrum of neurodevelopmental and epilepsy-associated disorders have been linked with mutations in the GABRA1 gene. However, the developmental, behavioral, and molecular mechanisms underlying GABRA1-associated epileptic disorders remain to be fully understood. Hence, the overarching goal of this dissertation is to investigate the behavioral …
Neurogenetic Function Of Host Cell Factor-1, Victoria Lynn Castro
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 …
Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger
Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger
Williams Honors College, Honors Research Projects
I made endospanin 1 knockout (KO) zebrafish to examine its effects on lipid and bone metabolism. Endospanin 1, or leptin receptor overlapping transcript (leprot), is a cytosolic protein linked to the protein hormone leptin that influences the trafficking of leptin receptors to the plasma membrane of cells. Genes for endospanin and tyrosinase (a pigmentation enzyme) were targeted via a microinjection of guide RNAs and CRISPR Cas9 into zebrafish embryos at 2-4 cell stages. I was able to disrupt the endospanin 1 gene (based upon the disruption of tyrosinase), but very few mutant zebrafish fully developed into adults. Only low KO …
Developmental Exposures To Pfas Mixtures Impair Elongation Of The Exocrine Pancreas In Zebrafish (Danio Rerio), Emily M. Formato
Developmental Exposures To Pfas Mixtures Impair Elongation Of The Exocrine Pancreas In Zebrafish (Danio Rerio), Emily M. Formato
Masters Theses
Poly- and perfluoroalkyl substances (PFAS) are a class of bioaccumulative toxicants used in numerous industrial and commercial products. Perfluorooctanesulfonic acid (PFOS) alters pancreatic organogenesis during development, and perfluorohexanesulfonic acid (PFHxS) has been suggested as a replacement for PFOS due to its shorter carbon chain, but they are often found together in surfactants, such as legacy aqueous film-forming foam. This study investigates how developmental exposures to a PFAS mixture (PFHxS + PFOS) impact the developing exocrine pancreas. Zebrafish embryos (Tg(ptf1a:GFP)) were exposed to 0.01% DMSO, or 8, 16, 32 μM PFHxS alone, 16 μM PFOS alone, and 8, 16, and 32 …
Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes
Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes
Electronic Thesis and Dissertation Repository
Pathogenic variants in the human PRR12 (Proline Rich 12) gene are associated with PRR12-related Neuroocular Syndrome. However, little is known about the gene/protein function. The zebrafish was utilized to address this, as its attributes place it as a premier model to study genes involved in human development and disease. In situ hybridization and RT-PCR of embryos and larvae, and qRT-PCR of adult tissues revealed the spatial and temporal distributions of the prr12 paralogues: prr12a and prr12b. Both paralogues were detected from the maternal and zygotic transcriptomes in a global and diffuse expression pattern, and there was enrichment …
Investigating The Role Of Chd7 And Sox11 In Retinal Cell Development And The Ocular Complications Of Charge Syndrome, Laura Krueger
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 Role Of Sox4 In Ocular Morphogenesis And Retinal Differentiation, Rebecca Petersen
The Role Of Sox4 In Ocular Morphogenesis And Retinal Differentiation, Rebecca Petersen
Theses and Dissertations--Biology
Visual impairment ranges from mild forms that can be corrected with glasses to more severe cases that result in permanent loss of vision. Microphthalmia, anophthalmia, and coloboma (collectively referred to as MAC) account for 11% of cases of pediatric blindness and are a result of improper ocular morphogenesis. Retinitis Pigmentosa (RP) is a retinal degenerative disease that affects 1 in 3000 people worldwide. It is a progressive disorder that initially begins with loss of vision in low light settings due to rod photoreceptor degeneration but progresses to complete blindness upon loss of cone photoreceptors. Currently, there is no cure for …
Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance, Kayla Titialii-Torres
Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance, Kayla Titialii-Torres
Theses and Dissertations--Biology
Hundreds of millions of people are affected by diabetes worldwide. Whether they are diagnosed with prediabetes or Type I or II diabetes, there are a variety of mechanisms in the pathogenesis of diabetes. Diabetes is a disease which consists of recurring states of hyperglycemia that can be difficult to manage due to either lack of insulin production or improper utilization of insulin. While these mechanisms of action differ, complications induced by diabetes occur in both poorly regulated Type I and II. Common complications of diabetes include nerve damage, kidney damage, and eye damage. Eye damage specifically is called diabetic retinopathy …
Activation Of Nrf2 At Critical Windows Of Development Alters Protein S-Glutathionylation In The Zebrafish Embryo (Danio Rerio), Emily G. Severance
Activation Of Nrf2 At Critical Windows Of Development Alters Protein S-Glutathionylation In The Zebrafish Embryo (Danio Rerio), Emily G. Severance
Masters Theses
Perturbation of cellular redox homeostasis to a more oxidized state has been linked to adverse human health effects such as diabetes and cancer. However, the impact of altering the regulation of redox homeostasis during development is not fully understood. Specifically, this project investigates the role of the Nrf2 antioxidant response pathway and its effect on glutathione (GSH; cellular redox buffer) at critical windows of development. To explore this, we used zebrafish embryos (Danio rerio) as a model due to the function of GSH and the Nrf2 being conserved among vertebrates. We exposed zebrafish embryos to three Nrf2 activators: two antioxidant …
Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy
Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy
Doctoral Dissertations
The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, …
The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle
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 …
Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone
Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone
Graduate Theses, Dissertations, and Problem Reports
Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …
Regulation Of Yolk Microtubule Dynamics By Dachsous Cadherins, Gina Danielle Castelvecchi
Regulation Of Yolk Microtubule Dynamics By Dachsous Cadherins, Gina Danielle Castelvecchi
Arts & Sciences Electronic Theses and Dissertations
The process of epiboly, or the thinning and spreading of a tissue, is a well-conserved morphogenetic process. As one of four conserved gastrulation cell movements, epiboly is important to help organize the overall body plan. Epiboly in zebrafish involves the thinning and spreading of the blastoderm originating from the animal pole to completely enclose the yolk. It is driven by a multitude of physical processes that involve the three cell types comprising the embryo: the yolk syncytial layer (YSL), enveloping layer (EVL), and deep cells. These physical aspects can be broadly described as involving cell-cell interactions through adhesion proteins, actomyosin …
The Role Of Homologous Cyclin B’S In The Cell Cycle And, In Their Absence, The Effect On Zebrafish Early Development, Tetiana Petrachkova
The Role Of Homologous Cyclin B’S In The Cell Cycle And, In Their Absence, The Effect On Zebrafish Early Development, Tetiana Petrachkova
Dissertations
Regulation of cell division is essential for normal embryo development. The Cyclins and their Cyclin-dependent kinases are key regulators controlling this process. In this thesis, I examine the role of cyclin B1 and cyclin B2 in zebrafish development. It is thought that both Cyclins are necessary for a cell to progress past the G2/M checkpoint into mitosis. First, I show that zygotic Cyclin B1 is essential for normal cell cycle progression, but not for cells to enter mitosis. Lack of zygotic Cyclin B1 in the early arrest mutant specter, which carries a nonsense mutation in the cyclin B1 gene, …
Exploring The Role Of Ccdc141 In Zebrafish Heart Development, Luci Strong
Exploring The Role Of Ccdc141 In Zebrafish Heart Development, Luci Strong
Honors Theses
Zebrafish are a good model organism in which to identify genes important for heart development because most human genes have a zebrafish ortholog and genes in zebrafish are relatively simple to modify. ccdc141 is a gene with unknown function, which we originally found to be highly expressed in cardiac cells in mouse embryos. In this project, we are seeking to determine the function of ccdc141 using zebrafish. To perform this experiment, we are targeting ccdc141 for mutation using CRISPR/Cas9. In this project we have analyzed ccdc141 to determine regions of conservation, designed CRISPR guides to target those regions (exon 2 …
Elucidating The Functional Location Of Platelet-Derived Growth Factor Receptor Alpha, Creation Of A Review Chapter On The Use Of Zebrafish In Studying Congenital Heart Defects, And Using 3d Printing To Create Laboratory Tools, Jaret Lieberth
Honors Theses
Congenital heart defects (CHDs) are currently the most prevalent form of birth defect in the United States. Their combined frequency and severity make necessary a deeper understanding of the molecular underpinnings guiding heart formation. The first major step in cardiac morphogenesis, cardiac fusion, involves the medial movement of bilateral populations of myocardial precursor cells to the embryonic midline, where they merge to form the primitive heart tube. Although crucial to subsequent organogenesis, the precise mechanisms governing cardiac fusion remain unknown. Previous studies have found that a mutation in platelet-derived growth factor receptor alpha (pdgfra), called refuse-to-fuse (ref), results …
Elucidating The Developmental Defects In Zebrafish Associated With The Cardiac Drug Verapamil, Blake Stephan Justis
Elucidating The Developmental Defects In Zebrafish Associated With The Cardiac Drug Verapamil, Blake Stephan Justis
MSU Graduate Theses
Birth defects are abnormalities in a developing organism that lead to a malformation in structure or function. Over half of birth defects have no determined cause; however, known causes occur by genetic anomalies, exposure to environmental agents (a.k.a. teratogens), or multifactorial reasons. To explain the unknown causes of birth defects, an area of focus in this study is to identify potential teratogens. Identifying these teratogens, is key to preventing future birth defects. An obvious source of teratogens in pregnant women would be that of pharmaceuticals. Thus, a main goal of this study is to identify drugs that cause birth defects. …
Siah-Mediated Ups Regulation Of The Development Of The Visual System In Zebrafish (Danio Rerio), Warlen Pereira Piedade
Siah-Mediated Ups Regulation Of The Development Of The Visual System In Zebrafish (Danio Rerio), Warlen Pereira Piedade
Theses and Dissertations--Biology
The eye is a complex organ responsible for vision that which formation depends on several intricate developmental steps. Vision for humans is responsible for the majority of its sensory interactions with the environment. Eye development can be divided into two critical stages: morphogenesis, which establishes the eye structure culminating with the fusion of the optic fissure, a transient cleft important for eye vascularization, and subsequently specification and differentiation of the retina to form every type of retinal neuronal cell, including photoreceptors, rods and cones. Developmental failure in either of these critical stages can lead to inherited congenital or age-related blinding …
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 …
Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara
Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara
Williams Honors College, Honors Research Projects
I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization. …
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 …
Effects Of Herbicides On Zebrafish Embryo Development And Viability, Kayla Ray King
Effects Of Herbicides On Zebrafish Embryo Development And Viability, Kayla Ray King
MSU Graduate Theses
Environmental contaminants are chemicals of anthropogenic origin that are found in water, soil, and air, and are harmful to a wide variety of organisms (ORD US EPA, 2018-a). One common group of contaminants are herbicides. Though herbicides are used to control unwanted vegetation in agriculture, aquatic organisms and humans may be exposed to these herbicides through run off into streams and rivers, by drinking contaminated water, by consuming treated crops, by direct exposure, or through bioaccumulation. Thus the effect of these herbicides on animals needs further investigation. In this study, I sought to determine whether six different herbicides, which have …
Biochemical And Functional Characterization Of Semaphorin6a-Plexina Signaling In Zebrafish Eye Development, Riley St. Clair
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 …
The Effects Of Bisphenol F On Embryonic Cardiac Output In Zebrafish, Kyle Monnot
The Effects Of Bisphenol F On Embryonic Cardiac Output In Zebrafish, Kyle Monnot
Williams Honors College, Honors Research Projects
Bisphenol F (BPF) is an analog compound of the xenoestrogen bisphenol A (BPA). BPA utilization has decreased dramatically due to its detrimental effects as an endocrine disrupter. In place of BPA, BPF is growing to be a ubiquitous chemical in epoxy resin manufacturing. Recent research has begun to investigate the possible endocrinal effects of BPF as an analog of BPA. This study was performed to examine the potential effects of BPF exposure on cardiac parameters of zebrafish (Danio rerio) embryos. Embryos were exposed to 50 µg/L BPF for 48 hours, and cardiac parameters (stroke volume, heart rate, and …
Investigating The Role Of Histidyl-Trna Synthetase In Zebrafish Nervous System Development, Ashley Waldron
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 …
Neurodevelopmental Roles Of Semaphorin6a/Plexina2 Signaling In Zebrafish, Sarah Elizabeth Emerson
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 …
Effect Of Arsenic Exposure On Early Eye Development In Zebrafish (Danio Rerio), Remy S. Babich
Effect Of Arsenic Exposure On Early Eye Development In Zebrafish (Danio Rerio), Remy S. Babich
Electronic Theses and Dissertations
Arsenic is a metalloid that contaminates drinking water supplies worldwide. Due to concerns for human health, the World Health Organization (WHO) and the U.S. Environmental Protection Agency (EPA) have established a safe level in drinking water of ≤ 10 ppb. Arsenic has been shown to have carcinogenic effects in humans at high and low doses. Chronic exposure may result in dermal conditions such as hyperkeratosis and hyperpigmentation. Recently, arsenic exposure has also been linked to lower IQ values in children. The effect of arsenic on neurogenesis, specifically eye development, has not been widely explored. This study aimed to examine the …
The Role Of Actr10 In Nervous System Development And Disease, Amy Herbert
The Role Of Actr10 In Nervous System Development And Disease, Amy Herbert
Arts & Sciences Electronic Theses and Dissertations
The vertebrate nervous system requires myelinating glia for the fast propagation of action potentials, as well as for vital trophic support to axons. Myelinating glia produce myelin, which is a lipid-rich, multi-lamellar sheath that surrounds axons and allows for rapid electrical signaling. In the central nervous system (CNS), myelin is produced by oligodendrocytes, while in the peripheral nervous system (PNS), Schwann cells perform this function. Although glia have historically been understudied compared to neurons, recent research has uncovered critical roles for glia in nervous system development and disease. Disruption to myelin or to the glial cells that generate myelin can …
Functional Characterization Of Scaffold Protein Shoc2, Hyein Jang
Functional Characterization Of Scaffold Protein Shoc2, Hyein Jang
Theses and Dissertations--Molecular and Cellular Biochemistry
Signaling scaffolds are critical for the correct spatial organization of enzymes within the ERK1/2 signaling pathway and proper transmission of intracellular information. However, mechanisms that control molecular dynamics within scaffolding complexes, as well as biological activities regulated by the specific assemblies, remain unclear.
The scaffold protein Shoc2 is critical for transmission of the ERK1/2 pathway signals. Shoc2 accelerates ERK1/2 signaling by integrating Ras and RAF-1 enzymes into a multi-protein complex. Germ-line mutations in shoc2 cause Noonan-like RASopathy, a disorder with a wide spectrum of developmental deficiencies. However, the physiological role of Shoc2, the nature of ERK1/2 signals transduced through this …