The Sakano Laboratory

The University of Tokyo
Graduate Schoool of Science
Department of Biophysics and Biochemistry

Yayoi 2-11-16, Bunkyo-ku, Tokyo 113-0032
Japan

Phone: 81-3-5689-7239
Fax: 81-3-5689-7240
E-mail: sakano@mail.ecc.u-tokyo.ac.jp

Research Interests of the Lab

We are interested in the choice of the odorant receptor (OR) genes and projection of olfactory sensory neurons (OSNs) in mouse.


Current Projects

Similar to the antigen receptor genes in lymphocytes, the mammalian OR genes are expressed in a mutually exclusive and monoallelic manner in OSN (one neuron one receptor rule). This forms the genetic basis for the neuronal identity of OSNs. DNA rearrangement has long been regarded of as a possible mechanism for the allelic exclusion of the OR genes. However, mice cloned from mature OSN nuclei expressed the full repertoire of ORs, and the possibility of irreversible gene translocation was excluded as a mechanism to activate a single OR gene in each OSN. How is it, then that allelic exclusion is achieved in the olfactory system? Our recent experiments indicated an inhibitory role of the functional OR protein in preventing further activation of other OR genes. We are currently trying to clarify the nature of feedback signals and their target molecules to ensure the one neuron one receptor rule.

It has been reported that OR molecules play a crucial role in projecting axons of OSNs to the olfactory bulb (OB). OSNs expressing a given OR gene converge their axons to a specific set of glomeruli on the OB. Thus, the olfactory signal received in the OE is converted to a topographic map of activated glomeruli on the OB. Our recent experiments indicated that each OR gene has a unique expression area in the OE, and that the dorsal/ventral arrangement of glomeruli on the OB is correlated with the expression areas of corresponding ORs along the dors-medical/ventro-lateral axis in the OE. In contrast, the anterior/posterior arrangement of glomeruli appears to be independent of the epitherial locations of OSNs, but more dependent on the expressed ORs. We are currently studying how the neuronal identity of an OSN is represented at the axon terminus in the process of OSN projection.


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