|Department Affiliations||Department of Molecular Biology and Genetics Department of Neuroscience|
|SOM Address||800 Preclinical Teaching Building|
The mammalian olfactory system provides an excellent model to study two of the important questions in molecular neurobiology. The continual replacement of olfactory receptor neurons mimics many aspects of neuronal differentiation and development in the brain. The olfactory system, therefore, provides a unique opportunity to observe processes in adults which, in other neuronal systems, only occur in the embryo. Additionally, the mammalian olfactory system has the remarkable ability to detect a wide variety of odorant molecules with high sensitivity and specificity. Olfactory acuity likely results from the contributions at the levels of anatomy, cellular structure and organization, biochemistry, genetics and neuronal connectivity. My laboratory has used biochemical and molecular genetic techniques to examine the mechanisms underlying development in the olfactory system, as well as the processes responsible for odorant detection. These studies have revealed an important role for genetic specialization in the olfactory system.
A major current effort in the laboratory focuses on the mechanisms that determine the patterns of expression of individual odorant receptor genes within the epithelium and the mechanism which control the pathways and eventual target cells chosen by those receptor neurons. We have identified transcription factors that likely coordinate the expression of key components in the outgrowth of neurons in mammals and C elegans. We have studied the mammalian olfactory system to elucidate the contributions of biochemistry, genetics and neural connectivity to sensitivity and specificity in olfactory signal transduction. We are continuing to characterize the molecular components of the second messenger pathways in olfactory and non-olfactory system. Major future directions will include the characterization of transcriptional activators that play a central role in neuronal differentiation. Finally, the molecular cloning of components of the olfactory signal transduction cascade, especially the receptor protein genes, has provided the essential tools to examine the processes which define the connections the olfactory neuroepithelium and the brain. We have also developed systems to express olfactory receptors in heterologous systems and determined ligands that activate several members of the family. Combined with other approaches in our laboratory, we hope to elucidate the principles of olfactory coding and odorant perception.
- Zhao, H. and Reed, R.R. (2001) X-Inactivation of the OCNC1 Channel Gene Reveals a Role for Activity-Dependent Competition in the Olfactory System. Cell 104: 651-660.
- Lewcock JW and Reed RR. (2004) A feedback mechanism regulates monoallelic odorant receptor expression. Proc Natl Acad Sci U S A. 101(4): 1069-74.
- Reed RR. (2004) After the holy grail: establishing a molecular basis for Mammalian olfaction. Cell.116(2): 329-36. Review
- Wang SS, Lewcock JW, Feinstein P, Mombaerts P, and Reed RR. (2004) Genetic disruptions of O/E2 and O/E3 genes reveal involvement in olfactory receptor neuron projection. Development 131(6): 1377-88.
- Kulaga HM, Leitch CC, Eichers ER, Badano JL, Lesemann A, Hoskins BE, Lupski JR, Beales PL, Reed RR and Katsanis N. (2004) Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nature Genetics 36(9): 994-8