Jill C. Wildonger
- Assistant Professor, Department of Biochemistry
- (608) 890-4619
Ph.D. Columbia University
Role of the microtubule cytoskeleton in creating and maintaining neuronal polarity during development
Neurons are functionally and structurally polarized, with distinct cellular projections that are specialized to receive and send signals (dendrites and axons, respectively). Axons and dendrites are essential for transmitting signals within a circuit, yet the molecular mechanisms that create these distinct neuronal structures have remained elusive. Our lab is addressing how neuronal polarity is created and maintained by focusing on the microtubule cytoskeleton, which has a dual function within cells: microtubules provide morphological structure and also serve as the major “highway” for the transport of proteins and organelles that are integral to neuronal function. We are characterizing the interplay between microtubules and the molecular motors dynein and kinesin, which transport cargo along microtubules to specific locations within neurons. By combining genetic, molecular, live-cell imaging and biochemical approaches, our goal is to delineate microtubule-based mechanisms implicated in neuronal polarity, using the developing fruit fly as a model. Indicative of the importance of the microtubule cytoskeleton in neuronal development, multiple human neurodevelopmental disorders, including classic lissencephaly, are linked to microtubule defects. One of our central goals is to identify the molecular and cellular causes of human disorders, such as classical lissencephaly, and determine how changes in the microtubule cytoskeleton impact neuronal structure and function.
Gratz, S.J., Cummings, A.M., Nguyen, J.N., Hamm, D.C., Donohue, L.K., Harrison, M.M.*, Wildonger, J.* and O’Connor-Giles, K.M.* (2013). Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genetics 113.152710; Early online May 24, 2013.
Zhu, S.†, Wildonger, J.†, Barshow, S.†, Younger, S., Huang, Y., and Lee, T. (2012). The bHLH repressor Deadpan regulates the self-renewal and specification of Drosophila larval neural stem cells independently of Notch. PLoS ONE 7: e46724.doi:10.1371/journal.pone.0046724.
Zhu, S., Barshow, S., Wildonger, J., Jan, L.Y. and Jan, Y.N. (2011). Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Drosophila larval brains. P.N.A.S. 108: 20615-20.
Wildonger, J., Jan, L.Y., and Jan, Y.N. (2008). The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels. Genes Dev. 22: 2447-53.
Zheng, Y.†, Wildonger, J.†, Ye, B., Zhang, Y., Kita, A., Younger, S.H., Zimmerman, S., Jan, L.Y., and Jan, Y.N. (2008). Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nat. Cell Bio. 10: 1172-80.
Wildonger, J., Sosinsky, A., Honig, B., and Mann, R.S. (2005). Lozenge directly activates argos and klumpfuss to regulate programmed cell death. Genes Dev. 19: 1034-9.
Wildonger, J., and Mann, R.S. (2005). The t(8;21) translocation converts AML1 into a constitutive transcriptional repressor. Development 132: 2263-72.
Wildonger, J., and Mann, R.S. (2005). Evidence that nervy, the Drosophila homolog of ETO/MTG8, promotes mechanosensory organ development by enhancing Notch signaling. Dev. Bio. 286: 507-20.
Ice, R.J.†, Wildonger, J.†, Mann, R.S. and Hiebert, S.W. (2005). Comment on “Nervy links Protein Kinase A to Plexin-mediated Semaphorin repulsion.” Science 309: 588.