National Insitute for Basic Biology

DIVISION OF SPECIATION MECHANISMS

Professor:
Tetsuo Yamamori
Our research goal is to understand mechanisms underlying evolution of the nervous system. To approach this question, we are currently focusing on two different subsystems which may respectively represent some molecular and cellular aspects of the system.

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

Recently, it has been recognized that cylokines, 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. Recent study have revealed that CDF/LIF and its receptors belong to the IL-6 family and the receptor family.

Bazen, first pointed out that the cyiokine receptor family may be evolved from an ancestral module of immunoglobulin (1990). Based on Bazen's model 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. 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 evolutional consideration predicts that the binding subunits generally determine the specificity of the receptors and it is possible that novel members of the cyiokine 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. It has been demonstrated by Ito and his colleagues (1982) that in the cerebellum the conjunctive stimuli of a parallel fiber 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).

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. Jun-B are predominantly induced around the local area where the AMPA and climbing fiber stimulation were conjuncted (Yamamori et al ., 1995; Neuroreport , in press). These results suggest that the coincidence mechanism may exist at gene expression level and lead to a cerebellar long-term plasticity.

Figure 1

Fig. 1.
Evolution of the IL-6 receptor family in the immune and nervous system (a Model). Modified from the figure 4 of Yamamori and Sarai (1994) including recent results from Hilton et al. (EMBO J., 13, 4765-4775, 1994.)

Figure 2

fig.2.
Gene Expression and Long-term Memory (a Model)

Publication List:

Yamamori, T. and Sarai, A. (1994) Evolution of the IL-6/class IB cyiokine receptor family in the immune and nervous systems. J. Physiology (Paris) . 88, 165-171.