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Full-Text Articles in Physiology

Wnt/_-Catenin Mediated Regulation Of Murine And Human Cardiac Electrophysiology And Arrhythmogenesis, Gang Li Aug 2020

Wnt/_-Catenin Mediated Regulation Of Murine And Human Cardiac Electrophysiology And Arrhythmogenesis, Gang Li

McKelvey School of Engineering Theses & Dissertations

Cardiac arrhythmias affects millions of Americans and can lead to sudden cardiac death, accounting for more than 300,000 deaths annually. Despite the vast knowledge available for cardiac disease and associated arrhythmias, very few effective therapies exist. Current interventions include cardioverter defibrillators and antiarrhythmic drugs targeting ion channels or the _-adrenergic pathway. In most acquired and inherited arrhythmias, molecular signaling pathways are perturbed. However, little is known about the underlying mechanism of how these signaling pathways regulate cardiac electrophysiology. Therefore, a better understanding of major signaling pathways governing cardiac development or dysregulated in cardiac disease could lead to novel therapeutics for …


The Effects Of Inhibiting Wnt Secretion And Activity On Cranial And Neural Development, Julie Louise Hulet Jun 2015

The Effects Of Inhibiting Wnt Secretion And Activity On Cranial And Neural Development, Julie Louise Hulet

Theses and Dissertations

Wnt signaling has been shown to have several roles in the development of sensory neurons, particularly in the ophthalmic portion of the trigeminal nerve. Many of these studies have relied on the conclusion that Wnt is necessary but not sufficient for the induction and maintenance of the neural precursor cells that develop in the ophthalmic placode. Wnt had been inhibited in the ophthalmic placode using a dominant negative t-cell factor (TCF) and resulted in the loss of Pax3 expression (indicative of undifferentiated placode cells) in all targeted cells, suggesting a loss of specification/commitment of these cells to the sensory neuron …


Regulation Of Dkk1, An Inhibitor Of The Wnt Signaling Pathway, By Dax-1 In Mouse Embryonic Stem Cells, Victor D. Gavallos Dec 2014

Regulation Of Dkk1, An Inhibitor Of The Wnt Signaling Pathway, By Dax-1 In Mouse Embryonic Stem Cells, Victor D. Gavallos

Undergraduate Honors Theses

DAX-1 is known to play a key role in the maintenance of pluripotency in mouse embryonic stem cells (mESC), such that elimination of DAX-1 (through methods such as RNAi) leads to the differentiation of ESC (Khalfallah et al. 2009). Earlier research by the Tzagarakis-Foster lab identified target genes of DAX-1 in mESC through PCR array methodology (Torres 2013). The Dickkopf 1 gene (Dkk1) was identified as a potential target of DAX-1 by these studies and has since been confirmed to be a DAX-1 target in mESC. However, to date very little is understood of the mechanism of DAX-1 repression of …


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 Role Of Wnt Signaling In Development Of The Ophthalmic Trigeminal Placode., Rhonda Nicole Lassiter Dec 2006

The Role Of Wnt Signaling In Development Of The Ophthalmic Trigeminal Placode., Rhonda Nicole Lassiter

Theses and Dissertations

Cranial placodes are ectodermal regions that contribute extensively to the vertebrate peripheral nervous system. The development of the ophthalmic trigeminal (opV) placode, which gives rise only to sensory neurons of the ophthalmic lobe of the trigeminal ganglion, is a well-studied model of sensory neuron development. While key differentiation processes have been characterized at the tissue and cellular levels, the molecules governing opV placode development have not been well described. This study identifies the canonical Wnt signaling pathway as a regulator of opV trigeminal placode development. Introducing dominant-negative TCF and dominant-active β-catenin expression constructs by in ovo electroporation, we have manipulated …


Fgf4 And Wnt5a/Pcp Signaling Promote Limb Outgrowth By Polarizing Limb Mesenchyme, Keri Lynn Low Nov 2006

Fgf4 And Wnt5a/Pcp Signaling Promote Limb Outgrowth By Polarizing Limb Mesenchyme, Keri Lynn Low

Theses and Dissertations

The focus of this study was to elucidate the molecular and cellular mechanisms whereby fibroblast growth factors (FGFs) mediate outgrowth of the limb. Specifically, we examined the epistatic relationship between FGF and Wnt/Planar cell polarity (PCP) signaling in establishing cell polarity as a mechanism for outgrowth. By implanting beads into embryonic limbs and lateral plate mesoderm, we established that FGF activates Wnt5a in a gradient fashion. Once it was established that Wnt5a was expressed at the right time and place to turn on PCP signaling, we investigated the ability of Wnt5a to influence cell migration and/or cell polarity. Our analysis …