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An In Vitro Microenvironment For Nucleus Pulposus Regeneration, Mark S. Shoukry
An In Vitro Microenvironment For Nucleus Pulposus Regeneration, Mark S. Shoukry
Graduate Theses, Dissertations, and Problem Reports
Intervertebral disc degeneration begins early in life, increases with age, and can ultimately result in disc failure. At the center of the disc, the nucleus pulposus (NP) resides in a hypoxic environment where degeneration is thought to begin. Initially, nucleus pulposus cells (NPCs) display altered morphology and function, along with increased rates of cellular senescence and apoptosis. Though no widely accepted treatment exists, autologous NP implantation techniques have shown promise. However, the process is flawed as a result of the long in vitro expansion required to obtain sufficient numbers of cells. Prolonged expansion on plastic produces negative changes such as …
Serum Response Factor Regulates Multiple Aspects Of Central Nervous System Development, Puo Yuan Lu
Serum Response Factor Regulates Multiple Aspects Of Central Nervous System Development, Puo Yuan Lu
All Theses and Dissertations (ETDs)
SRF is a highly evolutionary conserved activity-dependent transcription factor. Previous studies have shown that neuron-specific deletion of SRF results in deficits in tangential cell migration, guidance-dependent circuit assembly, activity-dependent gene expression, and synaptic plasticity in the hippocampus. However, very little is known in terms of whether SRF participates in earlier aspects of central nervous system development such as neuronal projection establishment, cell-fate specifications, and neural stem cell homeostasis and survival. We report that SRF is critical for development of major axonal tracts in the forebrain. Conditional mutant mice lacking SRF in neural progenitor cells: Srf-Nestin-cKO) exhibit striking deficits in cortical …
Mechanisms Of Early Brain Morphogenesis, Benjamen Filas
Mechanisms Of Early Brain Morphogenesis, Benjamen Filas
All Theses and Dissertations (ETDs)
In structures with obvious mechanical function, like the heart and bone, the relationship of mechanical forces to growth and development has been well studied. In contrast, other than the problem of neurulation: formation of the neural tube), developmental mechanisms in the nervous system have received relatively little attention. The central aim of this research is to characterize the biophysical mechanisms that shape the early embryonic brain. Experiments were performed primarily in the chicken brain, which is morphologically similar to humans during early stages of development. Proposed mechanisms were tested using computational models to ensure that hypotheses are consistent with physical …
The Importance Of Glucose Transport In Reproductive Events, Katie Adastra
The Importance Of Glucose Transport In Reproductive Events, Katie Adastra
All Theses and Dissertations (ETDs)
ABSTRACT OF THE DISSERTATION The Importance of Glucose Transport in Reproductive Events by Katie Lynn Adastra Doctor of Philosophy in Biology and Biomedical Sciences Developmental, Regenerative and Stem Cell Biology Washington University in St. Louis, 2012 Professor Kelle H. Moley, Chairperson Successful pregnancy outcome is contingent on a number of factors, the earliest of which include the events occurring during early pregnancy. This time period from fertilization to implantation requires drastic changes in both the embryo and the uterus, including cell proliferation and differentiation. Alterations in environment may lead to adverse effects during any of these stages. This emphasizes the …
Galnt11 Is A Novel Galnac-Transferase That Glycosylates Notch1 Receptor To Specify Between Motor And Sensory Ciliary Fates In The Vertebrate Left-Right Organizer, Marko Boskovski
Yale Medicine Thesis Digital Library
Heterotaxy is a disease of abnormal left-right (LR) body patterning associated with congenital heart disease that has very poor outcomes. Despite advances in surgical management, the two most severe forms of heterotaxy, right and left atrial isomerism, have a 29% and 64% 5-year survival rate, respectively. Through copy number variant analysis of heterotaxy patients, GALNT11 was recently identified as a novel gene important in human LR development. However, the mechanism by which Galnt11 causes heterotaxy has not been elucidated. In order to discover the mechanism of GALNT11 in patterning the LR axis, I performed loss of function and gain of …
Joint Functions Of Mett-10 And Dynein In The Caenorhabditis Elegans Germ Line, Maia Dorsett
Joint Functions Of Mett-10 And Dynein In The Caenorhabditis Elegans Germ Line, Maia Dorsett
All Theses and Dissertations (ETDs)
During normal development as well as in diseased states such as cancer, extracellular "niches" often provide cues to proximal cells and activate intracellular pathways. Activation of such signaling pathways in turn instructs cellular proliferation and differentiation. In the C.elegans gonad, GLP-1/Notch signaling instructs germ line stem cells to self renew through mitotic cell division. As germ cells progressively move out of the niche, they differentiate by entering meiosis and eventually form gametes. Using this model system, I uncovered a cooperative role for the METT-10 putative methyltransferase and the dynein motor complex in regulating the balance between germ cell proliferation and …
The Role Of Snail Homolog 1 In Embryonic Stem Cell Differentiation, Jennifer Gill
The Role Of Snail Homolog 1 In Embryonic Stem Cell Differentiation, Jennifer Gill
All Theses and Dissertations (ETDs)
During gastrulation, epiblast cells undergo an epithelial-to-mesenchymal transition: EMT) as they ingress through the primitive streak and form mesoderm. To better understand the molecular pathways of EMT during this developmental transition, we developed a model system utilizing mouse embryonic stem: ES) cells. We show that EMT occurs during ES cell differentiation and is dependent on the Wnt signaling pathway. We further show that the Wnt-dependent transcription factor Snail homolog 1: Snail) is expressed and capable of inducing EMT in differentiating ES cells. In addition to EMT, Snail accelerates differentiation, promotes mesoderm commitment, and restricts markers of primitive ectoderm and epiblast. …