Cell and Developmental Biology Commons^™

Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud

Theses and Dissertations

The serine/threonine kinase BRAF is a key part of the Ras-Raf-MEK-ERK pathway, an inducer of cell growth, differentiation, and survival. In humans, activating mutations, most commonly BRAF(V600E), have been detected in several cancers, including melanoma and thyroid cancer. In the Caenorhabditis elegans ortholog LIN-45, the equivalent mutation LIN-45(V627E) results in elevated Raf-MEK-ERK signaling. We performed an unbiased genetic screen to identify negative regulators of LIN-45(V627E). Here, we report the identification of the E3/E4 ubiquitin ligase UFD-2, and show it is a negative regulator of LIN-45 protein activity and levels. Loss of UFD-2 leads to accumulation of wild-type LIN-45 protein as …

Rab35 Centered Membrane Trafficking Pathway Directs Apical Constriction During Drosophila Gastrulation, Hui Miao

Electronic Theses and Dissertations

Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating high-tension contractile forces at the cell cortex before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be cellular processes to extract unidirectional changes that drive processive transformations in cell shape. During Drosophila melanogastergastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a …

Retinoic Acid Receptor Isoform-Specific Control Of Mouse Salivary Gland Development And Regeneration, Kara Desantis

Legacy Theses & Dissertations (2009 - 2024)

Controlled expansion and differentiation of progenitor cell populations is essential for organogenesis followed by continued maintenance of the population into and through adulthood. As the K5+ basal cell population is regulated by retinoic acid signaling, we interrogated the contribution of specific RAR isoforms to the regulation of these cells during submandibular salivary gland (SMG) organogenesis and regeneration. Retinoic acid has previously been shown to be involved in the development of the salivary gland, and recently, lack of retinoid signaling has been shown to impact the K5+ population of basal progenitor cells. Since retinoic acid is known to exert stimulatory effects …

Rna Sequencing Analysis Of The Developing Chicken Retina, Christophe Langouet-Astrie*, Annamarie Meinsen*, Emily R. Grunwald*, Stephen Turner, Raymond A. Enke

Ray Enke Ph.D.

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …

Effect Of Life History On Microrna Expression During C. Elegans Development, Xantha Karp, Molly Hammell, Maria C. Ow, Victor R. Ambros

Victor R. Ambros

Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs …

Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu

Theses and Dissertations

Elucidating the molecular mechanisms that play a role in cellular morphogenesis is critical to our understanding of brain development and function. The midbrain-hindbrain boundary (MHB) is one of the first folds in the vertebrate embryonic brain and is highly conserved across species. We used the zebrafish MHB as a model for determining the molecular mechanisms that regulate these cell shape changes. Cellular morphogenesis is tightly regulated by signaling pathways that rearrange the cytoskeleton and produce mechanical forces that enable changes in cell and tissue morphology. The generation of force within a cell often depends on motor proteins, particularly non-muscle myosins …

Guanosine Diphosphatase Is Required For Protein And Sphingolipid Glycosylation In The Golgi Lumen Of Saccharomyces Cerevisiae, Claudia Abeijon, Ken Yanagisawa, Elisabet Mandon, Alex Hausler, Kelley Moremen, Carlos Hirschberg, Phillips Robbins

Elisabet Mandon

Current models for nucleotide sugar use in the Golgi apparatus predict a critical role for the lumenal nucleoside diphosphatase. After transfer of sugars to endogenous macromolecular acceptors, the enzyme converts nucleoside diphosphates to nucleoside monophosphates which in turn exit the Golgi lumen in a coupled antiporter reaction, allowing entry of additional nucleotide sugar from the cytosol. To test this model, we cloned the gene for the S. cerevisiae guanosine diphosphatase and constructed a null mutation. This mutation should reduce the concentrations of GDP-mannose and GMP and increase the concentration of GDP in the Golgi lumen. The alterations should in turn …

Developmental Deregulation And Tumorigenesis Inhibition In 14-3-3zeta Knockout Mouse, Jun Yang

Dissertations & Theses (Open Access)

Cancer is second leading cause of death in the United States. Improving cancer care through patient care, research, education and prevention not only saves lives, but reduces health care cost as well. Breast cancer is the most leading cause of cancer incidence and cancer related death in women of the United States. 14-3-3s are a family of conserved proteins ubiquitously expressed in all eukaryotic organisms. They form complexes with hundreds of proteins by binding to specific phospho-serine/threonine containing motifs. In this way they regulate a variety of cellular processes and are involved in many human diseases especially cancer to our …

A Microrna Imparts Robustness Against Environmental Fluctuation During Development, Xin Li, Justin J. Cassidy, Catherine A. Reinke, Stephen Fischboeck, Richard W. Carthew

Faculty Publications

The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila , in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found …

Embryonic Expression Of Pre-Initiation Dna Replication Factors In Xenopus Laevis, Brian Walter, Jonathan Henry

Brian Walter

We examined the expression of various DNA replication factors, including: cdc45, the factors of the GINS heterotetramer (Sld5, Psf1, Psf2, Psf3), and PCNA, in Xenopus laevis during embryonic development via whole mount in situ hybridization. For the most part, these factors were expressed in similar patterns, with some subtle variations, throughout development within the anterior CNS, pharyngeal arches, and various placodes. More significant variations were also observed, including expression of only Psf1 and Psf2 in the pronephros and unique Psf2 expression in the somitic mesoderm. Overall, these results suggest that common regulatory mechanisms are involved in the transcriptional deployment of …

Xenopus Laevis Gelatinase B (Xmmp-9): Development, Regeneration, And Wound Healing, Brian Walter, Maria Carinato, Jonathan Henry

Brian Walter

It has been argued that matrix metalloproteinases play important roles in cellular differentiation and regeneration in certain systems. While studying changes in gene expression associated with the phenomena of cornea/lens transdifferentiation ("lens regeneration"), which takes place in the larva of Xenopus laevis, we identified the Xenopus gelatinase B gene. The open reading frame is homologous to other gelatinase B genes identified in other species and encodes all of the domains characteristic of this protein. Xenopus gelatinase B (Xmmp-9) is first expressed during early tail-bud stages in a subset of mesodermal cells scattered throughout the body. Expression is also seen in …