OF TOPOGRAPHIC PROJECTION IN THE LIMBIC SYSTEM BY THE EPH FAMILY MOLECULES.
Renping Zhou, Laboratory for Cancer Research, College of Pharmacy, Rutgers
University, Piscataway, NJ 08855.
Topographic projection is a general
feature of brain architecture and is critical for appropriate information
processing and coding. Nevertheless, little is known about the mechanisms
that govern topographic organization. Among the many regions exhibiting
topographic relations, the limbic system has been the focus of intense
interest, since it plays key roles in learning, memory, and motivated behavior.
The Eph family receptor tyrosine kinases and ligands have been recently
implicated in the specification of topographic maps. We have shown that
Eph family receptors and ligands are expressed in complementary fashion
in neurons and targets, respectively, in several regions of the limbic
system. For example, in the hippocampus, the Eph receptor Bsk is expressed
in an increasing lateral to medial gradient. In contrast, at least three
different ligands, Elf-1, LERK3/Ehk1-L, and AL-1/RAGS/LERK7, are transcribed
in complementary (opposing) gradients in the hippocampal subcortical target,
the lateral septum. However, the spatial and temporal distribution of the
ligands are different such that combinatorially they form a smooth dosromedial
to ventrolateral gradient in the lateral septum, specifying the full target
region during development. Consistent with a key role in hippocamposeptal
topographic projection, the ligands selectively inhibit the growth of the
topographically inappropriate medial hippocampal neurites but sustain the
growth of correct lateral neurites. Our studies indicate that the inhibitive
interaction of Bsk and its ligands restrict the receptor-positive medial
neurons to the topographically appropriate, ligand-poor dorsal septal target.
In addition to the hippocamposeptal system, BSK and its ligands are also
expressed in afferents and targets of neurons from several other regions
of the limbic system, including neurons in the mesolimbic pathway, which
arises from the ventral tegmental dopaminergic neurons and terminates in
the nucleus accumbens and limbic regions such as the amygdala. These observations
indicate that the Eph family molecules play important roles in establishing
the limbic neural circuits.
Titles] [Anderson] [Bolz] [Chugani] [Levitt] [Olson]