Faculty and Research
Faculty by Name
John Ngai
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John Ngai
Professor of Neurobiology*
*Coates Family Professor of Neuroscience, Helen Wills Neuroscience Institute; Head, Neuroscience Graduate Program
Research Interests
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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
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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. In one line of investigation, we are defining the odorant-binding properties of cloned fish odorant receptors, as fish respond to water soluble cues that are more amenable as probes for biochemical analyses. The zebrafish also offers advantages for studying development; methods for the generation and screening of mutant zebrafish may permit genetic approaches for studying odorant receptor gene expression and olfactory neurogenesis. Genomic mapping of odorant receptor genes and reveals that, as in other vertebrate species, odorant receptor genes are clustered in the zebrafish genome. However, genes tightly linked within a cluster are not coordinately regulated, suggesting that the regulation of individual receptor genes require the interaction of specific trans-acting factors with proximal cis-regulatory sequences. We are pursuing a variety of approaches, including transgenic manipulations, to define the promoter sequences responsible for directing the developmentally-regulated expression of the odorant receptor genes.
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 expressedin spatially-restricted patterns in the olfactory bulb; such molecules would be good candidates as guidance cues for ingrowing olfactory axons.
DNA microarrays. 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
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Molecular determinants of ligand selectivity in a vertebrate odorant receptor. [Luu, P., H.O. Bertrand, F. Acher, and J. Ngai (2003) Submitted for publication]
A spatial map of gene expression in the olfactory bulb. [D.M. Lin, Y.H. Yang, J.S. Scolnick, L.J. Brunet, V. Peng, Y. Okazaki, Y. Hayashizaki, T. Speed, and J. Ngai (2003) Submitted for publication]
Analysis of gene expression in the developing mouse retina. [E. Diaz, Y.H. Yang, T. Ferreira, K.C. Loh, M. Tessier-Lavigne, Y. Okazaki, Y. Hayashizaki, T.P. Speed, and J. Ngai (2003) Proc. Natl. Acad. Sci. USA 100, 5491-5496]
Molecular analysis of gene expression in the developing pontocerebellar projection system. [E. Diaz, Y. Ge, Y.H. Yang, K.C. Loh, Y. Okazaki, Y. Hayashizaki, T. Serafini, T.P. Speed, J. Ngai, and P. Scheiffele (2002) Neuron 36, 417-434]
Odorant receptor gene regulation: implications from genomic organization. [E. Kratz, J.C. Dugas, and J. Ngai (2002) Trends Genet. 18, 29-34]
Analysis and characterization of an odorant receptor gene cluster in the zebrafish genome. [J.C. Dugas and J. Ngai (2001) Genomics 71, 53-65]
Formation of precise synaptic connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity. [D.M. Lin, F. Wang, G. Lowe, G. H. Gold, R. Axel, J. Ngai, and L. Brunet (2000) Neuron 26, 69-80]
Functional identification of a goldfish odorant receptor. [D.J. Speca, D.M. Lin, P.W. Sorensen, E.Y. Isacoff, J. Ngai, and A.H. Dittman (1999) Neuron 23, 487-498]
Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed by dynamic imaging in living zebrafish embryos. [J. L. Dynes and J. Ngai (1998) Neuron 20, 1081-1091]
Last Updated 2004-09-20