Elizabeth Gavis
Systems and Circuits
Systems and Circuits

Damon B. Pfeiffer Professor in the Life Sciences, Professor of Molecular Biology.

Associated Faculty

Research: RNA localization and translational regulation during development in drosophila

gavis@princeton.edu
Research Lab
PDF icon elizabeth-gavis-2014-cv.pdf
609-258-3857
328 Moffett
609-258-1770
Faculty Assistant:
Matt Montondo
montondo@princeton.edu
609-258-266

Research Focus

Post-transcriptional control of neuronal development

The dendritic arbors of neurons have characteristic shapes, sizes, and branching patterns that influence how neurons receive, integrate, and respond to external signals. Understanding how dendritic arbors develop appropriately is thus critical to understanding neuronal function. Dendrite morphogenesis is a dynamic process involving outgrowth, branching, guidance, and in some cases remodeling. These events are genetically controlled and highly regulated to generate dendritic arbors suited to the appropriate task.

Whereas transcription factors have been shown to regulate the basic architecture of specific neuronal subtypes, transcriptional control may not be sufficient to change the proteome rapidly far from the cell body where dendrite outgrowth and branching occurs. Instead, post-transcriptional mechanisms like mRNA localization and on-site, on-demand mRNA translation afford local spatial and temporal control of gene expression and have been shown to play roles in dendritic arborization, spine formation, and pruning, as well as in synaptic plasticity associated with learning and memory. Accordingly, mutations in RNA-binding proteins (RBPs) have been linked to neuronal morphology defects associated with neurodegenerative and mental retardation disorders.

We study the role of post-transcriptional regulation and the effector RBPs in dendritic arbor development using a set of stereotypic Drosophila sensory neurons. These neurons, which fall into four classes with distinct morphologies, function in mechanosensation, proprioception, and nociception and provide a powerful model for investigating mechanisms that control dendrite morphogenesis and their outcome for animal behavior. Through RNAi and transposon tagging screens, we have identified numerous RBPs and localized RNAs involved in dendritic arbor development, and have shown how translational repression plays a neuroprotective role to maintain dendritic arbors. Current projects combine genetics, live and fixed imaging, and genome-level methodologies to identify RNA targets of key RNA-binding proteins and to decipher the mechanisms by which RNA-binding proteins modulate expression of cytoskeletal and cell adhesion proteins to control dendritic branching.


Selected Publications

  • Tenenbaum, C.M., Misra, M., Alizzi, R.A., and Gavis, E.R. (2017) Enclosure of dendrites by epidermal cells restricts branching and permits coordinated development of spatially overlapping sensory neurons. Cell Reports 20, 3043-3056. PMC5662031

  • Tenenbaum, C.M. and Gavis, E.R. (2016) Removal of Drosophila muscle tissue from larval fillets for immunofluorescence analysis of sensory neurons and epidermal cells. Journal of Visualized Experiments 117, e54670, doi:10.3791/54670. PMC5226124

  • Misra, M., Edmund, H., Schlueter, M.A., Marot, J.E., Tambasco, J., Ennis, D., Barlow, I., Sigurbjornsdottir, S., Mathew, R., Vallés, A.M., Davis, I., Leptin, M., and Gavis, E.R. (2016) Genome-wide screen for dendritically localized RNAs identifies genes required for dendrite morphogenesis. G3: Genes, Genomes, Genetics 6, 2397-2405. PMC4978894

  • Bhogal, B., Plaza-Jennings, A. and Gavis, E.R. (2016) Nanos-mediated repression of hid protects Drosophila larval sensory neurons after a global switch in sensitivity to apoptotic signals. Development 143, 2147-2159. PMC4920170

  • Olesnicky, E.C., Killian, D.J., Rathjen, A.R., Garcia, E., Sola, I.E., and Gavis, E.R. (2014) Extensive use of RNA binding proteins in Drosophila sensory neuron dendrite morphogenesis. G3: Genes, Genomes, Genetics 4, 297-306. PMC3931563

  • Xu, X., Brechbiel, J.L., and Gavis, E.R. (2013) Dynein-dependent transport of nanos RNA in class IV dendritic arborization neurons requires Rumpelstiltskin and the germ plasm organizer Oskar. Journal of Neuroscience 33, 14791-14800. PMC3771026

  • Thanawala, S., Rister, J., Goldberg, G., Zuskov, A. Olesnicky, E.C., Flowers, J., Purugganan, M., Gavis, E.R., Desplan, C. and Johnston, R. (2013) Regional modulation of a stochastically expressed factor determines ommatidial subtypes in the Drosophila retina. Developmental Cell 25, 93-105. PMC3660048

  • Olesnicky, E.C., Bhogal, B., and Gavis, E.R. (2012) Combinatorial use of translational co-factors for cell type specific regulation during neuronal morphogenesis in Drosophila. Developmental Biology 365, 208-218. PMC3642870

  • JayaNandanan, N., Gavis, E.R., Riechmann, V., and Leptin, M. (2011) A genetic in vivo system to detect asymmetrically distributed RNA. EMBO Reports 12, 1167-1174. PMC3207103

  • Menon, K., Andrews, S., Murthy, M., Gavis, E.R. and Zinn, K. (2009) The translational repressors Nanos and Pumilio have divergent effects on presynaptic terminal growth and postsynaptic glutamate receptor subunit composition. Journal of Neuroscience 29, 5558-5572. PMC2750846

  • Brechbiel, J.L. and Gavis, E.R. (2008) Spatial regulation of nanos activity is required for its function in dendrite morphogenesis. Current Biology 18, 745-750. PMC2474551

  • Ye, B., Petritsch, C., Clark, I.E., Gavis, E.R., Jan, L.Y., and Jan, Y.N. (2004) Nanos and pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Current Biology 14, 314-321.