NATIONAL INSITUTE FOR BASIC BIOLOGY

National Institute for Basic Biology

Division of Cell Fusion

(Adjunct)

Professor:
Hitoshi Sakano
Research Associates:
Akio Tsuboi (until November)
Kanae Muraiso (on leave)
Institute Research Fellow:
Hiroaki Kasai (until March)
Graduate Student:
Nika Yamazaki (from Tokyo Institute of Technology)


Recently, hundreds of odorant receptor (OR) genes have been reported in the olfactory system, although how the expression of this gene system is regulated has yet to be studied. It is assumed that only a limited number of the OR genes (possibly one) are activated in each olfactory neuron. In addition, neurons expressing a given OR gene are known to project their axons to a limited number of glomeruli at the fixed sites on the olfactory bulb.

We have been studying how individual neurons express a limited number of OR genes while keeping the rest of the genes silent, and how neurons expressing a given OR gene project their axons to a few subsets among the 2000 glomeruli within the olfactory bulb. In order to study the selective expression of the OR genes, we have been characterizing a P1 clone containing two highly related genes, MOR10 and MOR28. These genes are 92% homologous within their coding regions and linked in tandem on mouse chromosome 14. In situ hybridization has revealed that both genes are expressed in the same spatial zone within the olfactory epithelium, but never expressed simultaneously in the same neuron.

Developmental analyses have revealed that MOR10-expressing neurons appear earlier during embryogenesis than those MOR28-expressing. However, the number of MOR28 neurons is greater than that of MOR10 neurons after birth and continues to increase to a ratio of 2.5:1 by adulthood. These results suggest that individual olfactory neurons may activate OR genes through a stochastic mechanism even between two closely related OR genes; yet this selection appears to be biased in both the onset and level of expression. Interestingly, olfactory neurons expressing either MOR10 or MOR28 project their axons to two distinct, but adjacent subsets of glomeruli on the olfactory bulb. We conclude that two highly homologous and tandemly linked OR genes are expressed in a mutually exclusive manner in individual olfactory neurons, and that neurons expressing either of these genes project their axons to two discrete, but neighboring subsets of glomeruli on the olfactory bulb.

For the study of the mutually exclusive expression of OR genes, we have generated transgenic mice which are devised to express the MOR28 gene in every olfactory neuron under the control of the olfactory marker protein (OMP) promoter. Since the OMP gene is expressed in the mature neurons within the olfactory epithelium, the transgene is expected to be activated in all olfactory neurons. Recently, a transgenic line is found to express the OMP-MOR28 transgene in most of the mature neurons within the olfactory epithelium as well as within the vomeronasal organ. We believe that the study of such transgenic mice will give us new insight into the molecular mechanisms for OR gene expression, as well as for neuronal projection to the olfactory bulb.


Publication List:
Asai, H., Kasai, H., Matsuda, Y., Yamazaki, N., Nagawa, F., Sakano, H. and Tsuboi, A. (1996) Genomic structure and transcription of a murine odorant receptor gene: differential initiation of transcription in the olfactory and testicular cells. Bioche. Biophys. Res. Comm. 221, 240-247.

nibb-adm@nibb.ac.jp
Last Modified: 12:00, June 27, 1997