Mechanisms of Epithelial Patterning and Morphogenesis.
Abstract: Epithelial development requires coordination amongst all constituent cells. Cell fates must be organized in discrete spatial domains by coordinated patterns of gene expression. These patterns of gene expression must then coordinate cell shapes and behaviors to generate morphological diversity. My work has investigated two distinct mechanisms that ensure the robust patterning and morphoge... read morenesis of Drosophila epithelial tissues. By understanding how these mechanisms ensure high fidelity spatial and temporal control over fundamental cellular processes, we may gain insight into the dysregulation of these same processes in disease. Patterning of the Drosophila notum During patterning of the Drosophila notum, the bone morphogenetic protein (BMP) homolog Dpp acts from the posterior margin to help coordinate a checkerboard-like pattern of gene expression that subdivides the tissue into progressively finer domains. However, it is unclear whether this patterning cue is sufficient to fully pattern the notum. We found that the zinc finger odd-skipped family of genes is expressed at the anterior margin of the notum, and is required early in development for notum formation generally, and throughout development for normal anterior programs of gene expression. Further, ectopic pathway activity in the posterior is sufficient to induce an anterior specific program of gene expression across the tissue. These data suggest that the odd-skipped genes control an anterior organizer that coordinates with Dpp to robustly pattern the notum. Morphogenesis of the Drosophila pigment epithelium Cell shape change is considered to be driven by the regulation of E-Cadherin based adhesive forces, and opposing actomyosin based contractile forces. However, most work in vivo has focused on the role of actomyosin tension to constrict cell contacts during shape change. We investigated whether alternative pathways might contribute to contact maintenance or expansion. We found that contact length oscillates during cell shape change in the pigment epithelium. These length fluctuations occur at cell contacts under high levels of tension, and phases of contact expansion correlate with pulses of PIP3 and branched F-actin synthesis. Disruption of these pathways alters both cell shape and tissue organization. These studies suggest that branched F-actin dynamics might actively modulate tension in a field of cells undergoing extensive shape changes.
Thesis (Ph.D.)--Tufts University, 2014.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisor: Victor Hatini.
Committee: Karina Meiri, James Schwob, Peter Juo, and Adam Martin.
Keywords: Biology, and Developmental biology.read less