NATIONAL INSITUTE FOR BASIC BIOLOGY  


National Institute for Basic Biology

DIVISION OF SPECIATION MECHANISMS I


Professor:
Tetsuo Yamamori
Research Associates:
Yuriko Komine
Akiya Watakabe
Takashi Kitsukawa
Postdoctoral Fellow:
Rejan Vigot (JSPS)
Visiting Scientist:
Kimiko Yamamori
Yoshinori Shirai
Graduate student:
Shiro Tochitani
Katsusuke Hata
Yusuke Komatsu
Akishi Onishi (Kyoto University)
Shuzo Sakata (kyoto University)
Nobuaki Tanaka (Kyoto University)
Hiroshi Fujita (Kyoto University)
Ryohei Tomioka (Kyoto University)
Technical Staffs:
Hideko Utsumi



O ur research goal is to understand mechanisms underlying evolution of the nervous system. In order to approach this question, we are currently focusing on two systems.



I. Evolution of cytokine receptor families in the immune and nervous systems

It has been recognized that cytokines, defined as inter-cellular mediators in the immune system, have a variety of roles in the nervous system as well. One such a factor, LIF (leukemia inhibitory factor) known also as CDF (Cholinergic Differentiation Factor), is a pleiotropic factor which shows a remarkable repertoire of activities from embryonic stem cells to neurons (Yamamori, T., 1996). Recent study have revealed that CDF/LIF and its receptors belong to the IL-6 family and the receptor family.

B ased on Bazanšs model which predicted the cytokine receptor family as a member of immunoglobulin super gene family (1990) and the model of the interaction among the members of the IL-6 family (ligand) and the IL-6 receptor family (Taga and Kishimoto, 1992; Stahl and Yancopoulos, 1993), we proposed that the evolution of the IL-6/class IB receptor family may have occurred in at least two major steps (Yamamori and Sarai, 1994). Firstly, binding subunits of an IL-6 receptor and for a CDF/LIF receptor evolved and secondly, a third binding subunits of a CNTF receptor evolved. Our model predicts that the binding subunits generally determine the specificity of the receptors and it is possible that novel members of the cytokine family and their receptors exist in the nervous system. In order to prove this hypothesis, we are currently working to examine the expression pattern of the family in the nervous system.



II. Gene expression and cerebellar long-term plasticity

In order to know roles of the genes involved in long-term memory, we choose the cerebellum as a model system. In the cerebellum the conjunctive stimuli of parallel fibers and a climbing fiber to a Purkinje cell induce prolonged reduction of a synaptic efficacy between the paralleled fiber to the Purkinje cell (LTD; long-term depression, Ito et al., 1982).

Previously, we examined the expression of 10 immediate early genes (IEGs) including all the known Fos and Jun family in cerebellar slices under the pharmacological condition that cause long-term desensitization of the Purkinje cell to AMPA (a glutamate analogue). Among the IEGs examined, Fos and Jun-B were predominantly induced under the conjunctive condition (Nakazawa et al., 1993).

Recently, we have examined Jun-B expression in vivo under a conjunctive protocol of AMPA, a pharmacological substitute for parallel fiber stimulation, and climbing fiber stimulation via electric Inferior Olive stimulation. June-B are predominantly induced around the local area where the AMPA and climbing fiber stimulation were conjunct (Yamamori et al., 1995). These results suggest that the coincidence mechanism may exist at gene expression level and lead to a cerebellar long-term plasticity (Fig. 1).

Toward further confirming this hypothesis, we are currently identifying several molecules which are induced in Purkinje cells 3 hours after the conjunction in collaboration with Dr. Ryoji Yanošs group (Brain Science Institute, RIKEN). One of these genes is currently further being characterized. We are also examining the expression of the genes under different types of, cognitive and procedural, learning tasks.
D uring our attempt to isolate LTD-related genes, we accidentally found repetitive genes which were specifically expressed in the rat brain (Bsr: brain specific repetitive gene). To our surprise, the genes are only found in the rattus but no other species so far examined including murine species. Although we do not know the function of this new type of gene at the moment, it may play some important role in the rat brain and we hope further characterization of the gene reveals it.

Fig. 1
Expression of Bsr in the rat hippocampus. In situ hybridization with an antisense probe of Bsr.



Publication List
Komine, Y., Tanaka, N., Yano, R., Takai, S., Yuasa, S., Shiroishi, T., Tsuchiya, K., and Yamamori, T. (in press) A novel type of non-coding RNA expressed in the rat brain. Mol. Brain Res.


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Last Modified: 12:00, May 28, 1999