NATIONAL INSITUTE FOR BASIC BIOLOGY

National Institute for Basic Biology

Division of Speciation Mechanisms I

Professor:
Tetsuo Yamamori
Research Associates:
Satoshi Koike
Yuriko Komine
Akiya Watakabe
Institute Research Fellow:
Takashi Kitsukawa
Visiting Scientist:
Kimiko Yamamori
Graduate student:
Kotarou Torii (Hokuriku Advanced Technology and Science University)
Technical Staffs:
Hideko Utsumi
Miki Ida


Our 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.

Based on Bazan's 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.


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 characterizing several molecules which are induced in Purkinje cells 3 hours after conjunction and following Jun-B induction in collaboration with Dr. Ryoji Yano's group (Frontier Research program, RIKEN). Most of these genes are unknown genes and we expect that the characterization will bring us new information on the late process of cerebellar long-term plasticity.


Publication List
Yamamori, T. (1996) Immediately early gene expression. In "Coincidence detection in the nervous system" Eds by A. Konnerth, R.Y. Tsien, K. Mikoshiba and J. Altman, Human Frontier Science Program, Strasbourg, 118-121.
Yano, R, Nakazawa, K., Kado, R., Karachot, L., Mikawa, S., Ito, M., Komine, Y. and Yamamori, T. (1996) Cerebellar long-term plasticity and gene expression. In "Integrative and molecular approach to brain function" Proceeding of the Uehara Memorial Foundation Symposium (Eds by M. Ito, and Y. Miyashita), Elsevier, 35-44.
Yamamori, T. (1996) Leukemia inhibitory factor and phenotypic specialization. In "Chemical Factors in Neuronal Growth, Degeneration and Repair" (Ed by C. Bell), Elsevier, 265-292.

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