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Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Stanley J. Roux, Jr. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 1998. / Vita. Includes bibliographical references (leaves 190-217). Available also in a digital version from Dissertation Abstracts.

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Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 103-112).

Cell polarity is essential for cellular functions, growth, development, and formation of multicellular organisms. Cell polarization is often regulated during the cell division cycle. For instance, many cell types lose polarity and round up during mitosis, and then reestablish polarity after division. The fission yeast Schizosaccharomyces pombe is a model system for studying cell polarization. These unicellular rod-shaped cells grow by extension from their tips, and then stop growth during mitosis. Upon cytokinesis, they initiate growth from the old cell end and later in interphase, initiate growth at the second cell end in a process known as "new end take off" or NETO. NETO is regulated by polarity proteins tea1p and tea4p which are deposited by microtubules at the cell tips. How these proteins regulate cell polarity is not yet well understood. These polarity proteins are thought to function in recruiting other proteins, which leads to localized actin polymerization, membrane trafficking and cell wall assembly, leading ultimately to polarized cell growth at the cell tip. In this thesis, I report the characterization of a new polarity protein tea5p in fission yeast. I identified tea5p in a screen for new NETO mutants. Tea5p is a new component of the tea-protein polarity pathway. It resides at cell tips in complexes with the other polarity proteins tea1p and tea3p, and functions downstream of tea1p. Genetic interactions suggest that tea5p regulates polarized growth by regulating the small GTPase cdc42p and its activator gef1p. Tea5p is a pseudokinase that binds to the plasma membrane with its N terminus, and requires its kinase like domain for function. Together my results begin to establish a pathway that links microtubules to activation of cdc42p for regulation for polarized growth in S. pombe.

Dishevelled (Dvl) proteins are key transducers of Wnt signaling and are encoded by members of a multi-gene family in vertebrates. We report here divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression in the mouse. Moreover, we find that the expression patterns of Dvl genes in the chick diverge significantly from those of Xenopus. In addition, in hemichordates, one of the outgroups to chordates, we find that the one Dvl gene is dynamically expressed in a tissue-specific manner. Using knockdowns, we find that Dvl1 and Dvl2 are required for early neural crest specification and for somite segmentation. Most strikingly, we report a novel role for Dvl3 in the maintenance of differentiated muscle and the development of the Xenopus sclerotome. Together, these data demonstrate that that the expression patterns and developmental functions of specific Dvl genes have diverged significantly during chordate evolution. The planar cell polarity (PCP) signaling pathway is essential for embryonic development because it governs diverse cellular behaviors, and the "core PCP" proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the "PCP effector" proteins, such as Intu and Fuz, remain largely unstudied. These proteins are essential for PCP signaling, but they have never been investigated in a mammal and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice display neural tube defects, polydactyly, and skeletal dysmorphologies that stem from defective ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we establish a central role for Fuz in membrane trafficking, showing that Fuz is essential for apical trafficking of ciliogenesis factors in ciliated cells and also for exocytosis in secretory cells. We identify a novel, Rab-related small GTPase as an interaction partner for Fuz, and this GTPase also is essential for ciliogenesis and secretion. These results are significant because they provide novel insights into the mechanisms by which developmental regulatory systems like PCP signaling interface with fundamental cellular systems such as the vesicle trafficking machinery. / text

Thesis (Ph. D.)--University of Texas at Austin, 2009. / Title from PDF title page (University of Texas Digital Repository, viewed on Sept. 15, 2009). Vita. Includes bibliographical references.