Auld, Vanessa - University of British Columbia

研究领域

My research program investigates the roles that glia play in the development and function of the nervous system. Glia are known to fulfill a number of important functions during nervous system development. Glia help guide axon guidance, separate axons bundles in nerves and finally wrap and insulate their associated axons and nerves. However many of the molecules and signals that mediate these roles of glia have yet to be determined. This is important given the essential role that glia play in the nervous systems of all animals. Any mutation or disease that disrupts glial cell function or development results in disruption of nervous system function and can lead to paralysis or death of the animal. One approach to study molecular and cellular interactions that occur between glia and neurons during development is to use a genetic approach. The organism of choice for these studies is the fruit-fly, Drosophila melanogaster, because of the powerful genetic tools that can be applied to study the molecular interactions that occur during nervous system development. There are many parallels between the glia in of vertebrates and Drosophila and we have shown that many of the same molecular cues are conserved. For instance, we have shown that the glia of the peripheral nervous system in Drosophila are strikingly similar to the vertebrate peripheral glia (Schwann cells) in terms of morphology, developmental dynamics and molecular composition. We have shown that disruptions in the glia of the peripheral nervous system can lead to loss of nervous system function, neurodegeneration and death in Drosophila. We use a combination of genetics, molecular and cell biology to study glial genes that are expressed during the development of the embryonic nervous system. We are using the advantages of Drosophila genetics to create new mutations in glial genes that disrupt the formation of the peripheral nervous system. We are interested in multiple aspects of glial cell development and function: 1. What are the proteins that drive glia migration? 2. What causes the glial cells to ensheathe/wrap their associated axons? 3. What triggers the formation of the glial based blood-brain barrier? 4. What are the molecules that form the blood-brain barrier between glial cells and how do they interact?

近期论文

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Padash-Barmchi, M., G. Samarasekera, M.M. Gilbert, V.J. Auld, B. Zhang. 2016. Magi Is Associated with the Par Complex and Functions Antagonistically with Bazooka to Regulate the Apical Polarity Complex. PLoS One 11:e0153259 Link » Petley-Ragan, L.M., E.L. Ardiel, C.H. Rankin, V.J. Auld. 2016. Accumulation of Laminin Monomers in Drosophila Glia Leads to Glial Endoplasmic Reticulum Stress and Disrupted Larval Locomotion. Journal of Neuroscience 36: 1151-64 Link » Sharifkhodaei, Z., M. Padash-Barmchi, M.M. Gilbert, G. Samarasekera, T.A. Fulga, D. Van Vactor, V.J. Auld. 2016. The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184. Journal of Cell Science 129: 1477-89 Link » Xie X., M. Gilbert, M., L. Petley-Ragan, L., V.J. Auld. 2014. Loss of focal adhesions in glia disrupts both glial and photoreceptor axon migration in the Drosophila visual system. Development 141:3072-3083 Link » Padash-Barmchi M., K. Charish, J. Que, V.J. Auld. 2013. Gliotactin and Discs-large are co-regulated to maintain epithelial integrity. J Cell Sci 126:1134-1142 Link » Brink D.L., M. Gilbert, X. Xie, L, Petley-Ragan, V.J. Auld. 2012. Glial processes at the Drosophila larval neuromuscular junction match synaptic growth. PLoS One 7(5):e37876 Link » Xie X., V.J. Auld. 2011. Integrins are necessary for the development and maintenance of the glial layers in the Drosophila peripheral nerve. Development 138:3813-3822 Link » Padash-Barmchi M., K. Browne, K. Sturgeon, B. Jusiak, V.J. Auld. 2010. Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia. J Cell Sci 123: 4052-4062 Link » Schulte, J., K. Charish, J. Que, S. Ravn, C. MacKinnon, V.J. Auld. 2006. Gliotactin and Discs large form a protein complex at the tricellular junction of polarized epithelial cells in Drosophila. J Cell Sci 119: 4391-401 Venema, D.R., T. Zeev-Ben-Mordehai, V.J. Auld. 2004. Transient apical polarization of Gliotactin and Coracle is required for parallel alignment of wing hairs in Drosophila. Dev Biol. 275: 301-14 Schulte, J., U. Tepass, V.J. Auld. 2003. Gliotactin, a novel marker of tricellular junctions, is necessary for septate junction development in Drosophila. J Cell Biol. 161: 991-1000 Sepp, K.J. and V.J. Auld. 2003. Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development. J Neurosci. 23: 8221-30 Sepp, K.J., V.J. Auld. 2003. RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Development 130: 1825-35 Gilbert, M., Smith, J., Roskams, A-J. and Auld, V.J. 2001. Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth promoting class of macroglia. Glia 34: 151-164 Sepp, K., Schulte, J. and Auld, V.J. 2001. Glia direct sensory neuron guidance at the CNS/PNS boundary. Developmental Biology 238: 47-63 Sepp, K., Schulte, J. and Auld, V.J. 2000. Developmental dynamics of peripheral glia in the embryo of Drosophila melanogaster. Glia 30: 122-133 Sepp, K.J. and Auld, V.J. 1999. The use of targeted transposition to convert lacZ to GAL4 enhancer trap lines. Genetics 151: 1093-1101 Auld V.J., Fetter R.D., Broadie K. and Goodman C.S. 1995. Gliotactin, a novel transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in Drosophila. Cell 81: 757-767