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Jill Wildonger

Research

Cell polarity is integral to cell function. In the nervous system, the ability of a neuron to receive and send signals depends on the proper localization of proteins and organelles within the neuron. Our goal is to elucidate the mechanisms that govern the internal organization and structure of neurons that is essential to neuronal communication. We leverage an innovative combination of cell biology, genetics, and biochemistry to elucidate how the activity of molecular motors and microtubules create distinct signal-sending (axon) and signal-receiving (dendrite) compartments. We capitalize on the strengths of a fruit fly model system to precisely manipulate protein activity in vivo and to image neurons live in intact animals. We seek to obtain a molecules-to-cells understanding of how neuronal structure and function arise from the activity of molecular motors and microtubules.

How are the proteins and organelles important to neuronal function properly localized?

Sensory neurons perceive environmental stimuli via their dendrites. We are investigating how microtubule-based transport localizes sensory ion channels and organelles, such as Golgi. Our goal is to elucidate the molecular logic by which the molecular motors dynein and kinesin localize proteins and organelles selectively to dendrites and not the axon. Our long-term goal is to combine our analyses of trafficking with behavioral studies to reveal how intracellular transport impacts neuronal activity and animal behavior.

Form and Function: How is neuronal architecture generated?

Neurons, like other cells, contain a mix of stable and dynamic microtubules that underlie their exquisite structures. Although microtubule stability and dynamics must be precisely regulated, the mechanisms that balance these two populations in cells are poorly understood. We are investigating the role that tubulin post-translational modifications and microtubule-associated proteins play in this process. Interestingly, our recent findings suggest that microtubules have an integral role in creating neuron-type-specific morphologies.

Select Publications

  • Yang, S.Z., and J. Wildonger. 2020. Golgi Outposts Locally Regulate Microtubule Orientation in Neurons but Are Not Required for the Overall Polarity of the Dendritic Cytoskeleton. Genetics, 2:435-447. PMID: 32265236.
  • Coombes, C.E.*, H.A.J. Saunders*, A.G. Mannava, D.M. Johnson-Schlitz, T.A. Reid, S. Parmar, M. McClellan, C. Yan, S.L. Rogers, J.Z. Parrish, M. Wagenbach, L. Wordeman, J. Wildonger, and M.K. Gardner. 2020. Non-enzymatic Activity of the α-Tubulin Acetyltransferase αTAT Limits Synaptic Bouton Growth in Neurons. 2020. Current Biology, 30:610-623. PMID: 31928876.
  • Kelliher, M.T., H.A.J. Saunders, and J. Wildonger. 2019. Microtubule control of functional architecture in neurons. Current Opinion in Neurobiology, 57:39-45. PMID: 30738328.
  • Yan, C., F. Wang, Y. Peng, C.R. Williams, B. Jenkins, J. Wildonger, H.-J. Kim, J.B. Perr, J.C. Vaughan, M.E. Kern, M.R. Falvo, E.T. O’Brien, R. Superfine, J.C. Tuthill, Y. Xiang, S.L. Rogers, and J.Z. Parrish. 2018. Microtubule Acetylation Is Required for Mechanosensation in Drosophila. Cell Reports, 25:1051-1065. PMID: 30355484.
  • Kelliher, M.T., Y. Yue, A. Ng, D. Kamiyama, B. Huang, K.J. Verhey, and J. Wildonger. 2018. Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts. Journal of Cell Biology, 217:2531-2547. PMID: 29728423.
  • Bier, E., M.M. Harrison, K.M. O’Connor-Giles, and J. Wildonger. 2018. Advances in Engineering the Fly Genome with the CRISPR-Cas System. Genetics, 208:1-18. PMID: 29301946
  • Jenkins, B.V., H.A.J. Saunders, H.L. Record, D.M. Johnson-Schlitz, and J. Wildonger. 2017. Effects of mutating α-tubulin lysine 40 on sensory dendrite development. Journal of Cell Science, 130:4120-4131. PMID: 29122984.
  • Winding, M., M.T. Kelliher, W. Lu, J. Wildonger, and V.I. Gelfand. 2016. Role of kinesin-1–based microtubule sliding in Drosophila nervous system development. Proceedings of the National Academy of Science, 113: E4985-E4994. PMID: 27512046.
  • Akbari, O.S., H.J. Bellen, E. Bier, S.L. Bullock, A. Burt, G.M. Church, K.R. Cook, P. Duchek, O.R. Edwards, K.M. Esvelt, V.M. Gantz, K.G. Golic, S.J. Gratz, M.M. Harrison, K.R. Hayes, A.A. James, T.C. Kaufman, J. Knoblich, H.S. Malik, K.A. Matthews, K.M. O’Connor-Giles, A.L. Parks, N. Perrimon, F. Port, S. Russell, R. Ueda, and J. Wildonger. 2015. Safeguarding gene drive experiments in the laboratory. Science. 349:927-929. PMID: 26229113.
  • Gratz, S.J., M.M. Harrison, J. Wildonger, and K.M. O’Connor-Giles. 2015. Precise Genome Editing of Drosophila with CRISPR RNA-Guided Cas9. Methods in Molecular Biology, 1311:335-348. PMID: 25981484.
  • Arthur, A.L., S.Z. Yang, A.M. Abellaneda, and J. Wildonger. 2015. Dendrite arborization requires the dynein cofactor NudE. Journal of Cell Science, 128:2191-2201. PMID: 25908857.
  • Harrison, M.M., B.V. Jenkins, K.M. O’Connor-Giles, and J. Wildonger. 2014. A CRISPR view of development. Genes & Development, 28:1859-1872. PMID: 25184674.
  • Gratz, S.J., J. Wildonger, M.M. Harrison, and K.M. O’Connor-Giles. 2013. CRISPR/Cas9-mediated genome engineering and the promise of designer flies on demand. Fly, 7:249-255. PMID: 24088745.
  • Gratz, S.J., A.M. Cummings, J.N. Nguyen, D.C. Hamm, L.K. Donohue, M.M. Harrison, J. Wildonger, and K.M. O’Connor-Giles. 2013. Genome Engineering of Drosophila with the CRISPR RNA-Guided Cas9 Nuclease. Genetics, 194:1029-1035. PMID: 23709638.
  • Zheng Y.*, J. Wildonger* , B. Ye, Y. Zhang, A. Kita, S.H. Younger, S. Zimmerman, L.Y. Jan, and Y.N. Jan. 2008. Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nature Cell Biology, 10:1172-1180. PMID: 18758451.

Biography

Jill Wildonger received her Ph.D. in Neurobiology and Behavior from Columbia University and was a post-doctoral fellow at UCSF. Prior to moving to UCSD in 2021, Dr. Wildonger was a faculty member in the Biochemistry Department at the University of Wisconsin-Madison.

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