Open Access. Powered by Scholars. Published by Universities.®

Physiology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 31 - 60 of 85

Full-Text Articles in Physiology

Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen Dec 2013

Fgf4 Induced Wnt5a Gradient In The Limb Bud Mediates Mesenchymal Cell Directed Migration And Division, John C. Allen

Theses and Dissertations

The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. …


Beta-Amyloid Inhibition Of Alpha 7 Nicotinic Acetylcholine Receptors And Factors That Potentially Influence The Aî²/Nachr Interaction, Christopher L. Jacobsen Jul 2013

Beta-Amyloid Inhibition Of Alpha 7 Nicotinic Acetylcholine Receptors And Factors That Potentially Influence The Aî²/Nachr Interaction, Christopher L. Jacobsen

Theses and Dissertations

Alzheimer's disease (AD) is a neurodegenerative disorder that manifests in the form of deficiencies in cognitive processes such as memory and learning. The pathological features of AD include hyperphosphorylated tau proteins that form neurofibrillary tangles as well as senile plaques composed primarily of the peptide β-amyloid (Aβ). When present in high concentrations in the brain, Aβ inhibits certain subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) in the hippocampus. The effects of Aβ in the hippocampus have proven to be neurotoxic, resulting in reduced functionality of nAChRs and the subsequent death of neurons in the cholinergic pathway. The early stages of …


Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons Jul 2013

Susceptibility Of Apoptotic Cells To Hydrolysis By Spla2: Molecular Basis And Mechanisms Defined, Elizabeth Gibbons

Theses and Dissertations

Secretory phospholipase A2 hydrolyzes phospholipids at a lipid-water interface, resulting in pro-inflammatory products being released from cell membranes. Healthy cells are resistant to cleavage by this enzyme, but apoptotic cells become susceptible to its activity. Only bilayers with certain characteristics are able to be hydrolyzed. Most recently, studies in this lab have emphasized the idea that the biophysical state of the bilayer (in terms of lipid order, spacing, and fluidity) is relevant in determining the probability of one phospholipid escaping the membrane to be hydrolyzed. Prior to this study, it had been shown that apoptotic cells undergo biophysical alterations that …


A Model For Sensory Neuron Development By Fgf And Notch: A Multifactorial Approach, Jacob Eugene Voelkel Jun 2013

A Model For Sensory Neuron Development By Fgf And Notch: A Multifactorial Approach, Jacob Eugene Voelkel

Theses and Dissertations

The ophthalmic trigeminal placode (opV) exclusively gives rise to sensory neurons. A number of signaling pathways including Wnt, PDGF, FGF, and Notch are all involved in the progression of an undifferentiated cell in the opV placode to a proneural cell in the condensing opV ganglion. However, the regulatory relationships between these signal transduction pathways are still unknown. To determine if FGF activation acts to modulate Notch signaling in the sensory neurogenesis pathway, a novel multifactorial approach was employed: FGF signaling was inhibited in individual cells and globally with simultaneous inactivation of Notch signaling in chick embryos to investigate if FGF …


Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval Dec 2012

Long-Term Depression Of Excitatory Inputs To Gabaergic Neurons In The Ventral Tegmental Area, Philip J. Sandoval

Theses and Dissertations

Dopamine cells within the ventral tegmental area of the brain are involved in motivation and reward. Drugs of abuse target these dopamine cells altering their activity and plasticity resulting in addiction. While dopamine cell activity is primarily involved in addiction, the GABA neurons in the VTA have also been shown to have an indirect role. By decreasing the activity of the inhibitory GABA inputs onto dopamine neurons abusive drugs can indirectly increase dopamine cell activity resulting in addictive behaviors. However, although GABA neurons are important in the perception of reward, much less is known about how the excitatory inputs to …


Hormonal And Morphological Aspects Of Growth And Sexual Maturation In Wild-Caught Male Vervet Monkeys (Chlorocebus Aethiops Pygerythrus), Tegan J. Gaetano Dec 2012

Hormonal And Morphological Aspects Of Growth And Sexual Maturation In Wild-Caught Male Vervet Monkeys (Chlorocebus Aethiops Pygerythrus), Tegan J. Gaetano

Theses and Dissertations

Knowledge of baseline changes in testosterone (T) and other androgens is central to both investigations of morphological, physiological, and behavioral correlates of inter-individual variation in the timing and shape of key events and transitions over the life course and questions of the evolution of species-specific schedules of maturation in primates. T represents an important determinant of spermatogenesis in male mammals and plays a central role in the expression of male sexual behavior and the development of secondary sex characteristics. This research integrates hormonal and morphometric methods to determine age-related changes in fecal testosterone (fT) metabolites and morphological markers of sexual …


Regulation Of Sensory Neurogenesis In The Trigeminal Placode: Notch Pathway Genes, Pax3 Isoforms, And Wnt Ligands, Jason Samuel Adams Nov 2012

Regulation Of Sensory Neurogenesis In The Trigeminal Placode: Notch Pathway Genes, Pax3 Isoforms, And Wnt Ligands, Jason Samuel Adams

Theses and Dissertations

This dissertation is divided into three chapters, each discussing the study of different regulatory molecules involved in sensory neurogenesis occurring in the trigeminal placode. Chapter one is a spatiotemporal description of Notch pathway genes in chick opV placode by stage-specific expression analysis, showing expression of many Notch pathway genes and effectors in the opV placode. Notch pathway gene expression is primarily confined to the ectoderm with highest expression of these genes at the beginning stages of peak neuronal differentiation. This information preceded studies of the functional roles that Notch signaling has in the opV placode and how it may affect …


Membrane Properties Involved In Calcium-Stimulated Microparticle Release From The Plasma Membranes Of S49 Lymphoma Cells, Lauryl Elizabeth Campbell Aug 2012

Membrane Properties Involved In Calcium-Stimulated Microparticle Release From The Plasma Membranes Of S49 Lymphoma Cells, Lauryl Elizabeth Campbell

Theses and Dissertations

The mechanism of microparticle shedding from the plasma membrane of calcium-loaded cells has been investigated in erythrocytes and platelets. Recent studies have revealed the physiological and clinical importance of microparticle release from nucleated cells such as lymphocytes and endothelium. The experiments of this study were designed to address whether simple mechanisms discovered in platelets and erythrocytes also apply to the more complex nucleated cells. Four such mechanisms were addressed: potassium efflux, transbilayer phosphatidylserine migration, cytoskeleton degradation, and membrane lipid order. The rate and amount of microparticle release in the presence of a calcium ionophore, ionomycin, was assayed by light scatter …


Tissue Specific Porcupine Deletion Reveals A Novel Role For Ectodermal Wnts In Musculotendon Development, Aaron P. Smith Jul 2012

Tissue Specific Porcupine Deletion Reveals A Novel Role For Ectodermal Wnts In Musculotendon Development, Aaron P. Smith

Theses and Dissertations

The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the …


The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson Jun 2012

The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages. RAGE expression increases following ligand binding and when diverse cells are exposed to a variety of insults including cigarette smoke extract (CSE). The current research sought to characterize the pro-inflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity and fewer AMs in RAGE null mice compared to controls. Primary AMs were obtained from BAL, exposed to CSE in vitro, and RNA, DNA, …


Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill May 2012

Characterization Of Altered Epithelial Cell Turnover And Differentiation In Embryonic Murine Lungs That Over-Express Receptors For Advanced Glycation End-Products (Rage), Jeffrey Alan Stogsdill

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors highly expressed in the lung that modulate pulmonary inflammation during disease. However, the contributions of RAGE signaling are unknown during pulmonary organogenesis. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE in alveolar type II cells of the lung. When RAGE is over-expressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. Flow cytometry and immunohistochemistry employing cell-specific markers for various distal cell types demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation through …


Iron Deficiency Causes A Shift In Amp-Activated Protein Kinase (Ampk) Catalytic Subunit Composition In Rat Skeletal Muscle, John Merrill Apr 2012

Iron Deficiency Causes A Shift In Amp-Activated Protein Kinase (Ampk) Catalytic Subunit Composition In Rat Skeletal Muscle, John Merrill

Theses and Dissertations

To determine effects of iron deficiency on AMPK activation and signaling, as well as the AMPKα subunit composition in skeletal muscle, rats were fed a control (C=50-58 mg/kg Fe) or iron deficient (ID=2-6 mg/kg Fe) diet for 6-8 wks. Their respective hematocrits were 47.5% ± 1.0 and 16.5% ± 0.6. Iron deficiency resulted in 28.3% greater muscle fatigue (p<0.01) in response to 10 min of stimulation (1 twitch/sec) and was associated with a greater reduction in phosphocreatine (C: Resting 24.1 ± 0.9 micromol/g, Stim 13.1 ± 1.5 micromol/g; ID: Resting 22.7 ± 1.0 micromol/g, Stim 3.2 ± 0.7 micromol/g; p<0.01) and ATP levels (C: Resting 5.89 ± 0.48 micromol/g, Stim 6.03 ± 0.35 micromol/g; ID: Resting 5.51 ± 0.20 micromol/g, Stim 4.19 ± 0.47 micromol/g; p<0.05). AMPK activation increased with stimulation in muscles of C and ID animals. A reduction in Cytochrome c and other iron-dependent mitochondrial proteins was observed in ID animals (p<0.01). The AMPK catalytic subunit (alpha) was also examined because both isoforms are known to play different roles in responding to energy challenges. In ID animals, AMPK alpha2 subunit protein content was reduced to 71.6% of C (p<0.05), however this did not result in a significant difference in resting AMPK alpha2 activity. AMPK alpha1 protein was unchanged, however an overall increase in AMPK alpha1 activity was observed (C: 0.91 pmol/mg/min; ID: 1.63 pmol/mg/min; p<0.05). Resting phospho Acetyl CoA Carboxylase (pACC) was unchanged. This study indicates that chronic iron deficiency causes a shift in the expression of AMPK alpha subunit composition and potentially altered sensitivity to cellular energy challenges.


C-Met Initiates Epithelial Scattering Through Transient Calcium Influxes And Nfat-Dependent Gene Transcription, Peter R. Langford Dec 2011

C-Met Initiates Epithelial Scattering Through Transient Calcium Influxes And Nfat-Dependent Gene Transcription, Peter R. Langford

Theses and Dissertations

Hepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and migrating as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-Met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. This study addresses this shortcoming in a number of ways.A high-throughput in vitro drug screen was employed to identify proteins necessary in this HGF-induced signaling. Cells were tested for reactivity to HGF stimulation in a Boyden chamber assay. This tactic yielded several small molecules that block HGF-induced scattering, including a calcium channel blocker. Patch clamping was used …


Mechanisms Of Prenatal High-Salt "Fetal Programming" Resulting In Stress Hyperresponsiveness In The Adult Female Offspring In The Sprague Dawley Rat., Clinton L. Johnson Aug 2011

Mechanisms Of Prenatal High-Salt "Fetal Programming" Resulting In Stress Hyperresponsiveness In The Adult Female Offspring In The Sprague Dawley Rat., Clinton L. Johnson

Theses and Dissertations

Female offspring of Sprague-Dawley rats fed a high-salt diet (HS) during pregnancy show an enhancement of mean arterial pressure (MAP) and heart rate (HR) response to acute stress in adulthood compared to offspring whose mothers were fed a normal-salt diet (NS) [1]. In the present study, we first examined the expression of soluble epoxide hydrolase (SEH) protein in brain tissue. Whole brains were collected and SEH gene (EPHX2) mRNA and SEH protein expression were analyzed using RT-PCR and Western blot, respectively. mRNA levels were relatively decreased in high-salt rats (1.0 ± 0.32 NS vs 0.39 ± 0.07 HS, n=6). However, …


Calcineurin Is Required For Trpv1-Induced Ltd Of Ca1 Stratum Radiatum Interneurons, Tyron Deray Jensen Jul 2011

Calcineurin Is Required For Trpv1-Induced Ltd Of Ca1 Stratum Radiatum Interneurons, Tyron Deray Jensen

Theses and Dissertations

Learning and memory in the brain are thought to be dependent on synaptic plasticity. In response to sensory input, synapses can be strengthened or weakened, known as long-term potentiation or long-term depression (LTD), respectively. Transient receptor potential vanilloid 1 (TRPV1) has been shown to mediate a novel form of presynaptic LTD in hippocampal interneurons. TRPV1 is currently being heavily studied in the PNS and being targeted by pharmaceuticals for its anti-nociceptive and anti-inflammatory properties. However, much less is known regarding TRPV1 function in the CNS, including the signal mechanism mediating hippocampal LTD despite its obvious importance. Here we performed whole-cell …


The Effects Of Β-Amyloid On Α7 Nicotinic Acetylcholine Receptors Expressed In Xenopus Oocytes, Malia L. Anderson Jul 2011

The Effects Of Β-Amyloid On Α7 Nicotinic Acetylcholine Receptors Expressed In Xenopus Oocytes, Malia L. Anderson

Theses and Dissertations

The exact mechanism and progression of Alzheimer's disease (AD) at present is not fully understood. In patients suffering from AD, damage to the hippocampal region and impairment of learning and memory is present. It is also known that a buildup of β-amyloid plaques occur in AD patients and that β-amyloid interacts with some subtypes of neuronal nicotinic acetylcholine receptors (neuronal nAChRs). These receptors are composed of five subunits. The most prevalent nAChR subunit composition through the brain as a whole is α7. Previous data produced from our lab suggests that α7 nAChRs are also one of the most prevalent subunits …


Possible Molecular Mechanism To Account For Wavelength Dependence Of Equilibration Rates Of Patman And Laurdan In Phosphatidylcholine Bilayers, Hannabeth A. Franchino May 2011

Possible Molecular Mechanism To Account For Wavelength Dependence Of Equilibration Rates Of Patman And Laurdan In Phosphatidylcholine Bilayers, Hannabeth A. Franchino

Theses and Dissertations

Patman is a fluorescent membrane probe related to Laurdan. The structural distinctions between the two probes are the lengths of the aliphatic tails (eleven carbons in Laurdan and fifteen in Patman) and the presence of a trimethylammonium group on Patman that produces a positively-charged head. Preliminary studies exploring Patman as a probe to detect membrane properties during apoptosis revealed that the fluorescence intensity of two edges of the emission spectrum (435 and 500 nm) stabilizes at different rates as the probe binds to the cell membrane. To test whether these differences represent dissimilarities in probe binding to ordered and disordered …


Role Of Wnt5a And Possible Pathway Of Action Through Ror2 In Proximodistal Outgrowth Of The Limb, Tiffanie M. Dahl Mar 2011

Role Of Wnt5a And Possible Pathway Of Action Through Ror2 In Proximodistal Outgrowth Of The Limb, Tiffanie M. Dahl

Theses and Dissertations

Despite over 60 years of study, the molecular pathways and mechanisms governing limb outgrowth and patterning remain poorly understood. Fgfs expressed in the AER are known to be necessary and sufficient for proximodistal limb outgrowth and have been proposed to have a chemoattractive role. Wnt5a is a secreted factor which is expressed in a gradient in the distal limb with the highest concentration next to the AER. The presence of the AER is necessary to establish this gradient. Expression of Wnt5a in a concentration dependant manner can be induced in the limb through the implantation of a bead soaked in …


Proteoliposome Proton Flux Assays Establish Net Conductance, Ph-Sensitivity, And Functional Integrity Of A Novel Truncate Of The M2 Ion "Channel" Of Influenza A, Emily Peterson Nov 2010

Proteoliposome Proton Flux Assays Establish Net Conductance, Ph-Sensitivity, And Functional Integrity Of A Novel Truncate Of The M2 Ion "Channel" Of Influenza A, Emily Peterson

Theses and Dissertations

A novel truncate of Influenza A M2 protein (residues 22-62), incorporated into a uniquely tailored proteoliposome proton uptake assay, demonstrated proton flux more characteristic of an ion transporter than a traditional ion "channel." The liposome paradigm was essential for testing the conductance activity of this M2 truncate at a range of extraphysiological pHs appropriate for channel vs. transport function determination. In addition to transporter-typical proton flux, M2(22-62) showed the key characteristics of functional integrity: selective proton uptake into liposomes and block of uptake by amantadine. Two sets of proteoliposome proton flux assays were carried out, Set 1 at pH values …


Characterization Of The Lkb1-Mo25-Strad Ampkk Complex In Adult Mouse Skeletal Muscle, Cody Don Smith Nov 2010

Characterization Of The Lkb1-Mo25-Strad Ampkk Complex In Adult Mouse Skeletal Muscle, Cody Don Smith

Theses and Dissertations

In liver tissue, the AMP-activated protein kinase kinase (AMPKK) complex was identified as the association of LKB1, MO25α/β, and STRADα/β proteins; however, this complex has yet to be characterized in skeletal muscle. In this report, we demonstrate the expression of the LKB1-MO25-STRAD AMPKK complex in adult skeletal muscle, confirm the absence of mRNA splice variants, and report the relative mRNA expression levels of these complex-forming proteins. To facilitate this characterization we used control (ctrl) and muscle-specific LKB1 knockout (LKB1-/-) mice. LKB1 detection in untreated ctrl and LKB1-/- muscle lysates revealed two protein bands at approximately 50 and 60 kDa; although, …


Role Of Ampk In The Upregulation Of Steroidogenic Acute Regulatory Protein In The Zona Fasciculata Of The Adrenal Cortex, Adam Wesley Dayton Aug 2010

Role Of Ampk In The Upregulation Of Steroidogenic Acute Regulatory Protein In The Zona Fasciculata Of The Adrenal Cortex, Adam Wesley Dayton

Theses and Dissertations

Cortisol is a glucocorticoid produced by the zona fasciculata (ZF) of the adrenal cortex. Traditionally, cortisol production and release was seen as being regulated strictly by adrenocorticotropic hormone (ACTH). While this is true of baseline cortisol levels and in response to acute mental stress, the picture is somewhat more complicated in other situations.Interleukin-6 (IL-6) contributes to the maintenance of cortisol levels in situations of prolonged immune or inflammatory stress. AMP activated protein kinase (AMPK) was investigated as a possible mediator of the action of IL-6 or as an independent actor in raising cortisol levels in response to hypoxemic or hypoglycemic …


Chronic Amp-Activated Protein Kinase Activation And A High-Fat Diet Have An Additive Effect On Mitochondria In Rat Skeletal Muscle, Natasha Fillmore Jul 2010

Chronic Amp-Activated Protein Kinase Activation And A High-Fat Diet Have An Additive Effect On Mitochondria In Rat Skeletal Muscle, Natasha Fillmore

Theses and Dissertations

Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMPK, calcium, and circulating FFAs. Chronic treatment with either AICAR, a chemical activator of AMPK, or increasing circulating FFAs with a high fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high fat diet (HF), AICAR injections (AICAR), or a high fat diet and AICAR injections (HF+AICAR) for six weeks. At the end of …


Anti-Depressive And Anti-Obesity Changes Following Either Dietary Isoflavone Treatment Or Injection Treatment With The Isoflavonoid Equol: Positive Response Dependent On Animal Age And Ovarian Status In Female Long Evans Rats, Crystal Blake Jul 2010

Anti-Depressive And Anti-Obesity Changes Following Either Dietary Isoflavone Treatment Or Injection Treatment With The Isoflavonoid Equol: Positive Response Dependent On Animal Age And Ovarian Status In Female Long Evans Rats, Crystal Blake

Theses and Dissertations

Two conditions associated with ovarian depletion are increased potential for depressive episodes and increased abdominal weight gain. In five different experiments we examined the effect of soy-containing diets or equol injections on depression, serotonin levels, weight gain (BW) and white adipose tissue (WAT) deposition of female Long-Evans rats in various stages of life. Rats were intact, ovariectomized or experienced natural ovarian failure (NOF). While this paper will present each experiment, only experiment 5 is outlined here due to space limitations. From conception the rats were exposed to either a soy-rich (Phyto-600) or low-soy diet (Phyto-low). Animals experienced NOF at approximately …


Liver Kinase B1/Amp-Activated Protein Kinase Signaling In The Diaphragm, Jacob D. Brown Jun 2010

Liver Kinase B1/Amp-Activated Protein Kinase Signaling In The Diaphragm, Jacob D. Brown

Theses and Dissertations

The Liver Kinase B1 (LKB1)/AMP-Activated Protein Kinase (AMPK) signaling pathway is a major regulator of skeletal muscle metabolic processes. During exercise, LKB1-mediated phosphorylation of AMPK leads to its activation, promoting mitochondrial biogenesis and glucose transport, among other effects. The roles of LKB1 and AMPK have not been fully characterized in the diaphragm. Two methods of AMPK activation were used to characterize LKB1/AMPK signaling in diaphragms from muscle-specific LKB1 knockout (KO) and littermate control (C) mice: (1) acute injection of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and (2) 5-min direct electrical stimulation (ES) of the diaphragm. Diaphragms were excised 60 minutes post-AICAR injection and …


Molecular And Cellular Mechanisms Whereby The Apical Ectodermal Ridge (Aer), Via Wnt5a, Mediates Directional Migration Of The Adjacent Mesenchyme During Vertebrate Limb Development, Kate E. Kmetzsch Aug 2009

Molecular And Cellular Mechanisms Whereby The Apical Ectodermal Ridge (Aer), Via Wnt5a, Mediates Directional Migration Of The Adjacent Mesenchyme During Vertebrate Limb Development, Kate E. Kmetzsch

Theses and Dissertations

The vertebrate embryonic limb is a key model in elucidating the genetic basis underlying the three dimensional morphogenesis of structures. Despite the wealth of insights that have been generated from this model, many long-standing questions remain. For example, it has been known for over 70 years that the apical ectodermal ridge (AER) of the embryonic limb is essential for distal outgrowth and patterning of the adjacent limb mesenchyme. The mechanisms whereby the AER does accomplish outgrowth and patterning are still poorly understood. We propose that secreted FGFs from the AER activate Wnt5a expression in gradient fashion, which in turn provides …


Zyxin Regulates Epithelial-Mesenchymal Transition By Mediating Actin-Membrane Linkages At Cell-Cell Junctions, Liv Rebecca Sperry Aug 2009

Zyxin Regulates Epithelial-Mesenchymal Transition By Mediating Actin-Membrane Linkages At Cell-Cell Junctions, Liv Rebecca Sperry

Theses and Dissertations

Development is punctuated by morphogenetic rearrangements of epithelial tissues, including complete detachment of individual motile cells during epithelial-mesenchymal transition (EMT). Dramatic actin rearrangements occur as cell-cell junctions are dismantled and cells become independently motile during EMT. Characterizing dynamic actin rearrangements and identifying actin machinery driving these rearrangements is essential for understanding basic mechanisms of cell-cell junction remodeling; yet, neither the precise series of actin rearrangements at cell-cell junctions that accompany EMT, nor the machinery that controls actin rearrangement during EMT, have been identified. This work represents a detailed study of junctional actin reorganization in cells undergoing EMT, identifies actin regulatory …


Function Of The Notch/Delta Pathway In Ophthalmic Trigeminal Placode Development, Matthew K. Ball Jul 2009

Function Of The Notch/Delta Pathway In Ophthalmic Trigeminal Placode Development, Matthew K. Ball

Theses and Dissertations

The ophthalmic trigeminal placode (opV) is the birth place of one cell type of sensory neurons contributing to the trigeminal ganglion. Signals from the neural tube induce placodal identity within the surface ectoderm. Specified opV placode cells then up-regulate neuron differentiation markers and migrate to the ganglion. Several molecular pathways have been shown to act in opV placode cell development. Despite this, signals that specify individual neurons from within the opV placode remain unknown. However, it is known that components of the Notch signaling pathway are expressed in the opV placode. I tested the role of Notch signaling in opV …


The Effects Of Excess Corticosterone On Lkb1 And Ampk Signaling In Skeletal Muscle Of Rats, Gary N. Nakken Dec 2008

The Effects Of Excess Corticosterone On Lkb1 And Ampk Signaling In Skeletal Muscle Of Rats, Gary N. Nakken

Theses and Dissertations

Cushing's syndrome and glucocorticoid therapy lead to central obesity, insulin resistance, and symptoms of altered energy regulation similar to those observed in the metabolic syndrome. We hypothesized that excess glucocorticoids alter energy sensing/signaling in skeletal muscle through mediation of the LKB1/AMPK signaling pathway. To test this hypothesis, three 100 mg pellets of corticosterone were implanted subcutaneously in each of nine rats for two weeks. Responses were compared with sham operated controls fed ad libitum or food restricted to produce the body weights similar to the treatment group rats. After the treatment period, animals were anesthetized and the right gastrocnemius-plantaris and …


Determining The Role Of Wnt5a Signaling In Embryonic Limb Outgrowth Via Clonal Analysis, Whitney Herrod Sowby Aug 2008

Determining The Role Of Wnt5a Signaling In Embryonic Limb Outgrowth Via Clonal Analysis, Whitney Herrod Sowby

Theses and Dissertations

The exact mechanisms that regulate limb outgrowth the mouse embryo are unknown. Although there are several models, we favor a hypothesis where cells become polarized by signals secreted from the AER which orient their cell migration and/or divisions causing limb outgrowth. Clonal analysis has provided a mechanism to study cell behavior. We have generated a targeting construct containing the Fgf8 inhibitor, Sprouty2, in order to generate mutant clones for behavioral analyses in the limb. In order to more effectively study clonal behavior we report the modification of a novel clonal analysis approach, exo-utero surgery. We have modified, enhanced and proven …


Wnt5a Signaling Independently Of The Planar Cell Polarity Pathway Resulting In Convergent Extension And Neural Tube Closure During Vertebrate Development, Jared James Barrott Aug 2008

Wnt5a Signaling Independently Of The Planar Cell Polarity Pathway Resulting In Convergent Extension And Neural Tube Closure During Vertebrate Development, Jared James Barrott

Theses and Dissertations

Vertebrate development is regulated by cellular communication by mechanisms of cell fate and cell behavior. These crucial mechanisms are regulated by cellular signaling and in the case of cell fate, cellular signaling results in transcription of developmentally important genes. Communication between cells can also result in regulation of cell behavior by acting on cytoskeletal elements rather than nuclear factors. One of the cellular signals that regulate both cell fate and cell behavior is the family of Wnt signaling molecules. Wnt5a is one of 19 Wnt molecules and has been previously demonstrated to play critical roles in many important processes in …