John Ngai
Professor (Molecular & Cell Biology)
Email: jngai@socrates.berkeley.edu
Research areas: Cellular and Molecular Neuroscience, Cellular and Molecular Neuroscience, Developmental Neuroscience
Research Interests
How does the olfactory apparatus of vertebrates detect and discriminate thousands of odors? Our approach to elucidating the mechanisms of olfactory discrimination involves the characterization of odorant receptors and the neural pathways that they activate. We are also interested in the developmental mechanisms responsible for specifying odorant receptor expression in olfactory neurons and the pathfinding of these cells' axons to their appropriate targets. Finally, our lab is developing DNA microarray technologies to elucidate genome-wide patterns of gene expression in the nervous system.
Current Projects
The zebrafish olfactory system. The numerical and anatomical simplicity of the zebrafish olfactory system facilitates an analysis of the molecular and cellular basis of olfactory coding in a vertebrate species. We have used genome database mining to identify all the olfactory receptors encoded in the zebrafish genome and are using this information for functional studies. In one line of investigation, we are defining the odorant-binding properties of cloned fish odorant receptors, with the goal of understanding the molecular combinatorials used to identify different odorant compounds. The zebrafish also offers advantages for studying development. For example, it is possible to observe – in living embyros – labeled neurons as they differentiate and extend their axons to specific targets in the olfactory bulb. Thus, in another series of studies, we are developing transgenic zebrafish expressing GFP transgenes to follow the behaviors of specific olfactory neurons and their axonal processes.
Patterning in the olfactory bulb. Olfactory neurons expressing the same odorant receptor converge with great precision to a small number of glomeruli in the olfactory bulb. This suggests that spatial patterns of afferent innervation in the bulb are used to encode olfactory information. What are the mechanisms for specifying the pattern of olfactory neuron projections in the olfactory bulb? We are pursuing several complementary approaches to identify the molecules involved in olfactory axon pathfinding. Transgenic manipulations in the mouse and zebrafish are being used to assess the potential role of candidate genes in the formation of the olfactory sensory map. We are also utilizing DNA microarrays to search for molecules expressed in spatially-restricted patterns in the olfactory bulb; such molecules would be good candidates as guidance cues for ingrowing olfactory axons.
Gene expression analysis. Recent advances, which include the sequencing of entire genomes of selected model systems and the ability to survey "genome-wide" patterns of gene expression, now allow the dissection of biological processes at unprecedented levels of detail. We have established in our laboratory the full capabilities for carrying out DNA microarray analysis of gene expression. These techniques allow the analysis of mRNA expression from tens of thousands of genes at a time. To date, we have created high-density cDNA microarrays from the mouse and the zebrafish. We are using these microarrays as tools to investigate patterns of developmentally-regulated and spatially-restricted patterns of gene expression in the vertebrate central nervous system.
Selected Publications
Lin, D.M., Wang, F., Lowe, G., Gold, G. H., Axel, R., Ngai, J., and Brunet, L. 2000. Formation of precise synaptic connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity Neuron 26: 69-80.
Speca, D. J., Lin, D. M., Sorensen, P. W., Isacoff, E. Y., Ngai, J., and Dittman, A. H. 1999. Functional identification of a goldfish odorant receptor Neuron 23: 487-498.
Dynes, J. L. and Ngai, J. 1998. Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed by dynamic imaging in living zebrafish embryos Neuron 20: 1081-1091.
Diaz, E., Ge, Y., Yang, Y.H., Loh, K.C., Serafini, T., Okazaki, Y., Hayashizaki, Y., Speed, T.P., Ngai, J., and Scheiffele, P. 2002. Molecular analysis of gene expression in the developing pontocerebellar projection system Neuron 36: 417-434.
Diaz, E., Yang, Y.H., Ferreira, T., Loh, K.C., Tessier-Lavigne, M., Okazaki, Y., Hayashizaki, Y., Speed, T.P., and Ngai, J. 2003. Molecular patterning of the developing retina Proc. Natl. Acad. Sci. USA 100: 5491-5496.
Lin, D.M., Yang, Y.H., Scolnick, J.A., Brunet, L.J., Peng, V., Okazaki, Y., Hayashizaki, Y., Speed, T.P., and Ngai, J. 2004. A spatial map of gene expression in the olfactory bulb Proc. Natl. Acad. Sci. USA 101: 12,718-12,723.
Luu, P., Bertrand, H.O., Acher, F., Fan, J., and Ngai, J. 2004. Molecular determinants of ligand selectivity in a vertebrate odorant receptor J. Neurosci. 24: 10,128-10,137.
Alioto, T.S. and Ngai, J. 2005. The odorant receptor repertoire of teleost fish BMC Genomics 6: 173.
