Characterizing transcriptional and morphological consequences of long-term activity in a tonic C. elegans sensory neuron
Creators: name: Cohn, Jesse Aaron
Publisher: name: The University of Texas at Austin
Year: 2019
Subjects: Apoptosis
Plasticity

description: Two ways that long-term neural activity can affect a neuron are by altering the genes that the cell expresses, and by reshaping cellular architecture. These basic changes are imperative for neurons to continue to properly engage with their environment and with other cells. This dissertation outlines the use of the roundworm Caenorhabditis elegans as a tool to interrogate the effects of long-term activity on a tonic sensory neuron, specifically the primary oxygen-sensing neuron pair in the worm termed URXL/R. Described here are two cell-autonomous consequences of this prolonged sensory activity: the novel non-apoptotic transcription of a gene that typically causes cell death, and the growth of branches at the sensory ending of the neuron pair. Each of these projects sets the foundation for future work toward understanding the consequences of and genes that underlie these changes. Chapter Two focuses on the novel transcription of the pro-apoptotic gene egl-1 in URX in adults. EGL-1 is a member of the BH3-only family of proteins known for their role in inducing cell death. In C. elegans, egl-1 is normally transcribed in cells fated to die during development. Through the use of a forward genetic screen and environmental manipulations, we show that egl-1 is also transcribed in the URX neuron pair in adults as a result of prolonged oxygen sensation, and that this transcription does not induce cell death. We show that egl-1 transcription does not appear to contribute to any known URX function, and that its transcription is controlled by at least three pathways: one an unknown oxygen-dependent pathway, the other two comprised of the conserved protein kinases Protein Kinase G (PKG) and Salt-Inducible Kinase (SIK). Several BH3-only proteins in humans are expressed in the post-developmental nervous system without causing apoptosis, though their roles in these cells are largely mysterious, thus URX might provide a useful system for understanding aspects of non-apoptotic expression of BH3-only proteins in adult animals. In Chapter Three, we report that long-term exposure to surface-level oxygen (21%) causes the URX neuron pair to grow complex branching at its sensory dendritic ending. By studying mutants, we show that the oxygen sensory pathway is necessary for branch growth, and that the secondary messengers cGMP and calcium are both involved in this process. We also find that these dendritic branches are likely microtubule based, but do not contain a primary component of the oxygen sensation pathway. Accordingly, we also show that branch length and complexity do not correlate with changes in the cellular physiological or organismal behavioral response to oxygen. Therefore, though branches are grown in response to long-term oxygen exposure, they are unlikely to be involved in oxygen sensation per se. Finally, in Chapter Four, I suggest interesting future directions for each project and summarize my final thoughts.