Cell Biology & Molecular Genetics Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2750
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Item Development and the Early Animal Fossil Record: Evolution and Phylogenetic Applications(2016) Tweedt, Sarah Maureen; Delwiche, Charles F; Erwin, Douglas H; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Although evolutionary developmental biology and paleontology are linked by the study of morphology, the application of development to paleontological questions has only recently become more prominent. The growth of a robust developmental genetic framework for studying the origin and evolution of morphological features, however, holds great promise for understanding ancient animal life. As paleontology provides the historical record as well as the temporal and environmental context of past morphological evolution, uniting knowledge of developmental genetic systems with this historical record will form a key synthetic approach to understanding the early evolution of developmental processes. Ultimately unraveling the sequence of ancient animal developmental evolution will require combining analysis of comparative developmental data, critical assessment of fossil morphology within a developmental framework, and the targeted exploration of specific geologic periods to fill in the missing record of key times in animal developmental evolution. This study addresses each of these three approaches. First, I provide a new compilation and evaluation of recent comparative and experimental developmental biology data to review the nature of developmental ‘toolkits’ at the origin of the most basal animal clades. I reconstruct early animal developmental capacities and integrate these data within a temporal framework to better understand the context of earliest animal development. Second, I assess longstanding evolutionary hypotheses about the origin of the panarthropod clade and the phylogenetic position of Cambrian ‘lobopod’ fossils by examining signal present within current morphological datasets. I apply new methods to fossil panarthropod phylogeny estimation and suggest strategies for developmentally-informed phylogenetic coding of morphological data. Third, I present the discovery of the oldest spicule-bearing fossil sponges in the rock record, which co-occur in latest Ediacaran strata with classic enigmatic Ediacaran fauna. I provide a formal systematic description of fossil material from localities in both Nevada and southern Namibia. The combined approaches presented herein are a first step towards a deeper integration of developmental principles in the study and discovery of ancient animal life, and contribute to our understanding of the evolution of ancient animal developmental processes.Item Role and Regulation of Autophagy During Developmental Cell Death in Drosophila Melanogaster(2010) McPhee, Christina Kary; Mount, Stephen M; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Two prominent morphological forms of programmed cell death occur during development, apoptosis and autophagic cell death. Improper regulation of cell death can lead to a variety of diseases, including cancer. Autophagy is required for survival in response to starvation, but has also been associated with cell death. It is unclear how autophagy is regulated under specific cell contexts in multi-cellular organisms, and what may distinguish autophagy function during cell survival versus cell death. Autophagic cell death is characterized by cells that die in synchrony, with autophagic vacuoles in the cytoplasm, and phagocytosis of the dying cells is not observed. However, little is known about this form of cell death. Autophagic cell death is observed during mammalian development, during regression of the corpus luteum and involution of the mammary and prostate glands. Autophagic cell death is also observed during development of the fruitfly Drosophila melanogaster, during larval salivary gland cell death. Drosophila is an excellent genetic model system to study developmental cell death in vivo. Cells use two main catabolic processes to degrade and recycle cellular contents, the ubiquitin/proteasome system (UPS) and autophagy. Here I investigate the role of the UPS and autophagy in developmental cell death using Drosophila larval salivary glands as an in vivo model. Proteasome inhibitors are being used in anti-cancer therapies; however the cellular effects of proteasome inhibition have not been studied in vivo. Here I demonstrate that the UPS is impaired during developmental cell death in vivo. Taking a proteomics approach to identify proteins enriched in salivary glands during developmental cell death and in response to proteasome impairment, I identify several novel genes required for salivary gland cell death, including Cop9 signalsome subunit 6 and the engulfment receptor Draper. Here I show that the engulfment receptor Draper is required for salivary gland degradation. This is the first example of an engulfment factor that is autonomously required for self-clearance. Surprisingly, I find that Draper is cell-autonomously required for autophagy during cell death, but not for starvation-induced autophagy. Draper is the first factor to be identified that genetically distinguishes autophagy that is associated with cell death from cell survival.