No description available.

Includes bibliographical references (p. 142-157) / 1 v. : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates how Drosophilia Cyclin E transcription is regulated during developent, as a basis for determining how developmental signals control cell proliferation during Drosophila development. / Thesis (Ph.D.)--University of Adelaide, Depts. of Biochemistry and Genetics, 1998?

No description available.

No description available.

Not available / text

No description available.

A neuron’s function depends critically on the shape, size, and territory of its dendritic field. We have only recently begun to understand how diverse dendritic arbors are built and how the morphology and territory of these arbors support diverse neural functions. In this thesis, I use the Drosophila larval peripheral nervous system (PNS) as a model for studying these questions, as these neurons are very amenable to genetic manipulation and in vivo imaging. First, I examined the relationship between dendritic fields and sensory activity in the proprioceptive neurons of the body wall. In collaboration with Elizabeth Hillman’s lab, we used a high-speed volumetric microscopy technique, Swept Confocally Aligned Planar Excitation (SCAPE) microscopy, to simultaneously image the dendrite deformation dynamics and sensory activity of body wall neurons in crawling Drosophila larvae. We imaged a set of proprioceptive neurons with diverse dendrite morphologies and territories, revealing that each neuron subtype responds in sequence during crawling. These activities could conceivably provide a continuum of position encoding during locomotion. Activity timing is related to the dynamics of each neuron’s dendritic arbors, suggesting arbor shape and targeting endow each proprioceptor with a specific role in monitoring body wall deformation. Furthermore, our results provide new insights into the body-wide activity dynamics of the proprioceptive system, which will inform models of sensory feedback during locomotion. To investigate how dendritic arbors are built to support sensory function, I focused on proprioceptive (class I) and touch-sensing (class II-III) dendritic arborization (da) neurons. Proprioceptive and touch-sensing dendrite territories tend to target non-overlapping, neighboring, areas of the body wall. How is territory coverage specified during development, and how does this coverage support a specific sensory function? Ablation studies indicate that repulsive interactions between heterotypic dendrites are not required for territory patterning. Instead, dendrite boundaries correlate with Anterior (A)-Posterior (P) compartment boundaries in the underlying epidermal substrate: proprioceptive class I dendrites target the P compartment, while touch-sensing dendrites tend to avoid that region. I found that genetic expansion of the P compartment leads to expansion of class I proprioceptive dendrites, suggesting compartmentalized epidermal cues instruct dendrite targeting. Furthermore, SCAPE imaging revealed that the P compartment coincides with a major body wall fold that occurs during crawling. These results support a model in which dendrite targeting by compartment cues reliably tunes neurons for predictable stimuli on the body wall: proprioceptive dendrites target areas that bend predictably during crawling, while touch-sensing dendrites could be avoiding those areas to be tuned for external mechanosensory stimuli. To investigate the molecular identity of the substrate cues guiding the compartmental organization of dendrites, I tested candidate cues and sought new potential cues. I first tested cues that are known to be expressed in a compartmental fashion (Hedgehog and EGFR pathways). Interestingly, the overall dendrite territory footprint of class I proprioceptive cells is unaffected by known compartment cues. To reveal new candidates, I performed cell sorting and RNA sequencing. I identified 290 cell surface and secreted molecules with differential expression in the A and P compartments. I provide initial findings from a knockdown and misexpression screen testing the role of these candidates for class I and class III territory patterning. Taken together, these results provide new insights into how dendritic fields are patterned to support proper neural function.

Miniature neurotransmission is the trans-synaptic process where single synaptic vesicles spontaneously released from presynaptic neurons induce miniature postsynaptic potentials. Since their discovery over 60 years ago, miniature events have been found at every chemical synapse studied. However, the in vivo necessity for these small-amplitude events has remained enigmatic. In this thesis, I show that miniature neurotransmission is required for the normal structural maturation of Drosophila glutamatergic synapses in a developmental role that is not shared by evoked neurotransmission. Conversely, I find that increasing miniature events is sufficient to induce synaptic terminal growth. I show that miniature neurotransmission acts locally at terminals to regulate synapse maturation via a Trio guanine nucleotide exchange factor (GEF) and Rac1 GTPase molecular signaling pathway. My thesis study establishes that miniature neurotransmission, a universal but often-overlooked feature of synapses, has unique and essential functions in vivo.

No description available.

The nuclear lamina is a filamentous network that underlies the nuclear envelope. Lamina components include the family of LEM domain (LEM-D) proteins, named for LAP2, emerin and MAN1. Mutations in genes encoding LEM-D proteins cause tissue-restricted human disease, even though these genes are globally expressed. To understand the contributions of the LEM-D proteins to nuclear lamina function, investigations of the Drosophila LEM-D proteins was undertaken. The Drosophila genome encodes four LEM-D proteins and this thesis describes work done on the Drosophila homologues of MAN1 and emerin, Drosophila MAN1 (dMAN1) and Otefin (Ote). Chapter 2 describes the generation and phenotypic analyses of dMAN1 mutants. These mutants display a range of tissue-specific defects associated with an increase in BMP/Dpp signaling. This suggests that dMAN1 downregulates BMP/Dpp signaling at the nuclear periphery. Chapter 3 describes the identification and phenotypic analyses of ote mutants. Loss of Ote is associated with a tissue-specific defect of the female germline where ote mutant females display defects in germline stem cell (GSC) maintenance. Loss of Ote causes defects in the germline cells, the cap cells of GSC niche and an increased sensitivity to Dpp signaling in both germline and somatic cells. These findings support models suggesting that laminopathies arise from dysfunction of the homeostasis in stem cell populations. Taken together, these studies suggest that the nuclear lamina may play tissue-specific roles through regulation of signal transduction pathways. Our data also support the use of Drosophila as a system to elucidate the mechanistic basis of diseases associated with defects in the nuclear lamina.