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Glial Control Of Synapse Assembly At The Drosophila Neuromuscular Junction: A Dissertation, Kimberly S. Kerr Sep 2012

Glial Control Of Synapse Assembly At The Drosophila Neuromuscular Junction: A Dissertation, Kimberly S. Kerr

GSBS Dissertations and Theses

Emerging evidence in both vertebrates and invertebrates is redefining glia as active and mobile players in synapse formation, maturation and function. However, the molecular mechanisms through which neurons and glia interact with each other to regulate these processes is not well known. My thesis work begins to understand how glia use secreted factors to modulate synaptic function. We use Drosophila melanogaster, a simple and genetically tractable model system, to understand the molecular mechanisms by which glia communicate with neurons at glutamatergic neuromuscular junctions (NMJs). We previously showed that a specific subtype of glia, subperineurial peripheral glia cells (SPGs), establish dynamic ...


A Role For C-Jun Kinase (Jnk) Signaling In Glial Engulfment Of Degenerating Axons: A Dissertation, Jennifer M. Macdonald Jun 2012

A Role For C-Jun Kinase (Jnk) Signaling In Glial Engulfment Of Degenerating Axons: A Dissertation, Jennifer M. Macdonald

GSBS Dissertations and Theses

The central nervous system (CNS) is composed of two types of cells: neurons that send electrical signals to transmit information throughout the animal and glial cells. Glial cells were long thought to be merely support cells for the neurons; however, recent work has identified many critical roles for these cells during development and in the mature animal. In the CNS, glial cells act as the resident immune cell and they are responsible for the clearance of dead or dying material. After neuronal injury or death, glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ...


Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee Dec 2011

Intestine Homeostasis And The Role Of Tumor Suppressor Gene 101 In Drosophila Melanogaster: A Dissertation, Madhurima Chatterjee

GSBS Dissertations and Theses

Tissue homeostasis in the adult Drosophila melanogaster intestine is maintained by controlling the proper balance of stem cell self-renewal and differentiation. In the adult fly midgut, intestinal stem cells (ISCs) are the only dividing cells and their identity maintenance is crucial to the proper functioning of the fly gut. Various pathways such as Notch, JAK-STAT and Wingless are known to regulate ISC division and differentiation.

Here I used a pathogen feeding model to study conditions that accelerate ISC division and guide intestinal cell differentiation favoring enterocyte development. I also examined the role of Tumor Suppressor Gene 101 (TSG101) in ISC ...


Neuronal Diversification In The Postembryonic Drosophila Brain: A Dissertation, Suewei Lin Aug 2011

Neuronal Diversification In The Postembryonic Drosophila Brain: A Dissertation, Suewei Lin

GSBS Dissertations and Theses

A functional central nervous system (CNS) is composed of numerous types of neurons. Neurons are derived from a limited number of multipotent neural stem cells. Previous studies have suggested three major strategies nature uses to diversify neurons: lineage identity specification that gives an individual neural stem cell distinct identity based on its position in the developing CNS; temporal identity specification that gives neurons derived from a neural stem cell distinct identities based on their birth-order within the lineage; and binary cell fate specification that gives different identities to the two sister postmitotic neurons derived from the terminal division of a ...


Identification Of A Command Neuron Directing The Expression Of Feeding Behavior In Drosophila Melanogaster: A Dissertation, Thomas F. Flood May 2011

Identification Of A Command Neuron Directing The Expression Of Feeding Behavior In Drosophila Melanogaster: A Dissertation, Thomas F. Flood

GSBS Dissertations and Theses

Feeding is one of the most important behaviors for an animal’s survival. At a gross level, it is known that the nervous system plays a major role in the expression of this complex behavior, yet a detailed understanding of the neural circuits directing feeding behavior remains unknown. Here we identify a command neuron in Drosophila melanogaster whose artificial activation, using dTrpA1, a heat-activated cation channel, induces the appearance of complete feeding behavior. We use behavioral, genetic, cellular and optical imaging techniques to show that the induced behavior is composed of multiple motor programs and can function to uptake exogenous ...


Drosophila Pirna Function In Genome Maintenance, Telomere Protection And Genome Evolution: A Dissertation, Jaspreet S. Khurana Oct 2010

Drosophila Pirna Function In Genome Maintenance, Telomere Protection And Genome Evolution: A Dissertation, Jaspreet S. Khurana

GSBS Dissertations and Theses

Upon fertilization, the early embryo sustains most of the cellular processes using the maternally deposited reserves in the egg itself until the zygotic gene expression takes charge. Among the plethora of essential components provided by the mother are small non-coding RNAs called PIWI-interacting RNAs (piRNAs), which provide immunity to the zygote against transposon challenge. In this thesis, I have presented three different functions of piRNAs in Drosophila melanogaster- in maintenance of genomic integrity, telomere protection and their role as an adaptive immune system against genomic parasites.

In Chapter 2, I have described the phenotypic effects of the loss of piRNA ...


A View Of The Imd Pathway From The Rhim, Kamna Aggarwal Mar 2010

A View Of The Imd Pathway From The Rhim, Kamna Aggarwal

GSBS Dissertations and Theses

Innate immunity is the first line of defense against invading pathogens. It functions to eliminate pathogens and also to control infections. The innate immune response is also important for the development of pathogen-specific adaptive immune responses. As a result, the study of innate immune signaling pathways is crucial for understanding the interactions between host and pathogen. Unlike mammals, insects lack a classical adaptive immune response and rely mostly on innate immune responses.

Innate immune mechanisms have been widely studied in the fruit fly, Drosophila melanogaster. The genetic and molecular tools available in the Drosophila system make it an excellent model ...


Systems Level Processing Of Memory In The Fly Brain: A Dissertation, Michael Jonathan Krashes May 2009

Systems Level Processing Of Memory In The Fly Brain: A Dissertation, Michael Jonathan Krashes

GSBS Dissertations and Theses

Understanding the mechanisms of memory is vital in making sense of the continuity of the self, our experience of time and of the relation between mind and body. The invertebrate Drosophila melanogaster offers us an opportunity to study and comprehend the overwhelming complexity of memory on a smaller scale. The work presented here investigates the neural circuitry in the fly brain required for olfactory memory processing. Our observation that Dorsal Paired Medial (DPM) neurons, which project only to mushroom body (MB) neurons, are required during memory storage but not for acquisition or retrieval, led us to revisit the role of ...


Small Rna Sorting In Drosophila Produces Chemically Distinct Functional Rna-Protein Complexes: A Dissertation, Michael D. Horwich Jun 2008

Small Rna Sorting In Drosophila Produces Chemically Distinct Functional Rna-Protein Complexes: A Dissertation, Michael D. Horwich

GSBS Dissertations and Theses

Small interfering RNAs (siRNAs), microRNAs (miRNAs), and piRNAs (piRNA) are conserved classes of small single-stranded ~21-30 nucleotide (nt) RNA guides that repress eukaryotic gene expression using distinct RNA Induced Silencing Complexes (RISCs). At its core, RISC is composed of a single-stranded small RNA guide bound to a member of the Argonaute protein family, which together bind and repress complementary target RNA. miRNAs target protein coding mRNAs—a function essential for normal development and broadly involved in pathways of human disease; small interfering RNAs (siRNA) defend against viruses, but can also be engineered to direct experimental or therapeutic gene silencing; piwi ...


Mitotic Response To Dna Damage In Early Drosophila Embroyos: A Dissertation, Seongae Kwak Apr 2008

Mitotic Response To Dna Damage In Early Drosophila Embroyos: A Dissertation, Seongae Kwak

GSBS Dissertations and Theses

DNA damage induces mitotic exit delays through a process that requires the spindle assembly checkpoint (SAC), which blocks the metaphase to anaphase transition in the presence of unaligned chromosomes. Using time-lapse confocal microscopy in syncytial Drosophila embryos, we show that DNA damage leads to arrest during prometaphase and anaphase. In addition, functional GFP fusions to the SAC components MAD2 and Mps1, and the SAC target Cdc20 relocalize to kinetochore through anaphase arrest, and a null mad2mutation blocks damage induced prometaphase and anaphase arrest. We also show that the DNA damage signaling kinase Chk2 is required for damage induced metaphase ...


Dissecting Small Rna Loading Pathway In Drosophila Melanogaster: A Dissertation, Tingting Du Jan 2008

Dissecting Small Rna Loading Pathway In Drosophila Melanogaster: A Dissertation, Tingting Du

GSBS Dissertations and Theses

In the preceding chapters, I have discussed my doctoral research on studying the siRNA loading pathway in Drosophila using both biochemical and genetic approaches. We established a gel shift system to identify the intermediate complexes formed during siRNA loading. We detected at least three complexes, named complex B, RISC loading complex (RLC) and RISC. Using kinetic modeling, we determined that the siRNA enters complex B and RLC early during assembly when it remains double-stranded, and then matures in RISC to generate Argonaute bearing only the single-stranded guide. We further characterized the three complexes. We showed that complex B comprises Dcr-1 ...


Quantitative Analysis Of Hedgehog Gradient Formation Using An Inducible Expression System: A Dissertation, Vivian F. Su Nov 2006

Quantitative Analysis Of Hedgehog Gradient Formation Using An Inducible Expression System: A Dissertation, Vivian F. Su

GSBS Dissertations and Theses

The Hedgehog (Hh) family of proteins are secreted growth factors that play an essential role in the embryonic development of all organisms and the main components in the pathway are conserved from insects to humans. These proteins affect patterning and morphogenesis of multiple tissues. Therefore, mutations in the Hh pathway can result in a wide range of developmental defects and oncogenic diseases. Because the main components in the pathway are conserved from insects to humans, Drosophilahas been shown to provide a genetically tractable system to gain insight into the processes that Hh is involved in.

In this study, the ...


Genetic Dissection Of The Neural Circuitry Underlying Memory Stability In Drosophila: A Dissertation, Alex Carl Keene Aug 2006

Genetic Dissection Of The Neural Circuitry Underlying Memory Stability In Drosophila: A Dissertation, Alex Carl Keene

GSBS Dissertations and Theses

Understanding how memory is formed requires looking beyond the genes involved to the neural circuitry and temporal aspects of memory. In this dissertation I have focused my investigation on Dorsal Paired Medial (DPM) neurons, two modulatory neurons essential for memory in Drosophila. DPM neurons highly express the amnesiac (amn) gene, which encodes for a putative pre-pro-neuropeptide. amn function in DPM neurons is required for memory. Here I provide evidence that DPM neurons are cholinergic and that acetylcholine (ACh) and AMN act as co-transmitters essential for DPM function. In order to investigate the temporal requirements of DPM output I blocked transmitter ...


Biochemical Mechanism Of Rna Interference In Higher Organisms: A Dissertation, Dianne S. Schwarz Aug 2005

Biochemical Mechanism Of Rna Interference In Higher Organisms: A Dissertation, Dianne S. Schwarz

GSBS Dissertations and Theses

RNA interference (RNAi) is an evolutionarily conserved, sequence-specific gene silencing pathway found in eukaryotes, in which 21-nucleotide, small interfering RNAs (siRNAs) guide destruction of a corresponding target mRNA. RNAi is a natural mechanism for both genome surveillance and gene regulation. Moreover, siRNAs can be transfected into cultured mammalian cells, causing the sequence-specific ‘knock down’ of an mRNA. My work in the Zamore lab has centered around the Drosophilain vitro system and cultured mammalian cells to study the RNA interference (RNAi) pathway. small interfering RNAs (siRNAs) are incorporated into the RNA-induced silencing complex (RISC), which culminates in the cleavage of ...