- Molecular Biology
Neurons are highly polarized cells, with specialized dendritic and axonal processes. Our research focuses on how such structural and functional polarity is generated during development, using Drosophila as a model system. Localized protein synthesis, controlled through the localization of messenger RNAs (mRNAs), is a well established mechanism for generating cellular asymmetries and for functional specialization of polarized cells like neurons . mRNA localization typically involves recognition of mRNA localization signals embedded in mRNAs by localization factors, packaging of mRNA-protein complexes into transport particles, transport of these particles, and finally anchoring at the target destination. Silencing of translation during transport ensures that proteins are specifically produced on site.
We have shown that elaboration of the highly branched dendritic trees of a subset of larval sensory neurons requires the translational regulators Nanos and Pumilio. Nanos and Pumilio form a translational repression complex that first identified by its role in development of the embryonic anterior-posterior body axis. The complex must be limited to the embryo posterior and this is accomplished through the selective synthesis of Nanos from posteriorly localized nanos mRNA. We recently found that the function of Nanos/Pumilio in dendrite morphogenesis requires dendritic localization of nanos mRNA. Thus, our results suggest that Nanos is a local regulator of translation in the peripheral nervous system. We are using genetic, biochemical, and imaging methods to investigate how RNAs like nanos are packaged and transported as translationally silent particles and then locally translated. Other areas of interest include identifying mRNAs that are regulated by Nanos and Pumilio in sensory neuron dendrites for proper dendrite morphogenesis, investigating roles for Nanos and Pumilio in development of other neurons, including neuromuscular junction morphogenesis, and characterizing requirements for other RNA-binding proteins in neuronal development.
Weil, T.T., Parton, R., Davis, I., and Gavis, E.R. (2008) Changes in bicoid mRNA anchoring highlight conserved mechanisms during the oocyte-to-embryo transition. Curr. Biol. 18, 1055-1061.
Jain, R.A. and Gavis, E.R. (2008) The Drosophila hnRNP M homolog Rumpelstiltskin regulates nanos mRNA localization. Development 135, 973-982.
Brechbiel, J.L. and Gavis, E.R. (2008) Spatial regulation of nanos is required for its function in dendrite morphogenesis. Curr. Biol. 18: 745-750.
Gavis, E.R., Chatterjee, S., Ford, N.R., and Wolff, .LJ. (2008) Dispensability of nanos mRNA localization for abdominal patterning but not for germ cell development. Mech. Dev. 125, 81-90.
Weil, T.T., Forrest, K.M., and Gavis, E.R. (2006) Localization of bicoid mRNA in late oocytes is maintained by continual active transport. Dev. Cell 11, 251-262.
Kalifa, Y., Huang, T., Rosen, L.N., Chatterjee, S., and Gavis, E.R. (2006) Glorund, a Drosophila hnRNP F/H homolog, is an ovarian repressor of nanos translation. Dev. Cell 10, 291-301.
Duchow, H.K., Brechbiel. J.L., Chatterjee. S., and Gavis, E.R. (2005) The nanos translational control element represses translation in somatic cells by a Bearded box-like motif. Dev. Biol. 282, 207-217.
Forrest, K.M., Clark, I.E., Jain, R.A., and Gavis, E,R. (2004) Temporal complexity within a translational control element in the nanos mRNA. Development 131, 5849-5857.
Ye, B., Petritsch, C., Clark, I.E., Gavis, E.R., Jan, L.Y., Jan, Y.N. (2004) Nanos and Pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Curr. Biol. 14, 314-321.
Forrest, K.M. and Gavis, E,R. (2003) Live imaging of endogenous RNA reveals a diffusion and entrapment mechanism for nanos mRNA localization in Drosophila. Curr. Biol. 13, 1159-1168.