Journal of Neuroscience, Vol 14, 3437-3448, Copyright © 1994 by Society for Neuroscience
Calcium wave fronts that cross gap junctions may signal neuronal death during development
LR Wolszon, V Rehder, SB Kater and ER Macagno
Department of Biological Sciences, Columbia University, New York, New York 10027.
Embryonic anterior pagoda (AP) neurons in the leech interact with their
segmental homologs in adjacent ganglia through transient axons that overlap
during a critical period of development and then retract. However, when an
AP neuron is ablated mechanically or by irradiation during this period, an
adjacent homolog responds by reinitiating growth of its overlapped axon and
thereby taking over vacated territory (Gao and Macagno, 1987b; Gao, 1989).
The death of an AP cell is therefore communicated to its homolog, but the
mechanism underlying this signaling is presently unknown. Since it was
recently found that AP homologs are electrically and dye coupled through
their transient axons (Wolszon et al., 1994), we investigated the
possibility that gap junctions may mediate the cell death signal that could
occur between developing neurons. Among several candidate intercellular
signals, we began by studying calcium dynamics in embryonic AP cells, in
situ, since calcium is known to cross gap junctions and is implicated in
cell death in many systems. We found that elements that usually increase
[Ca2+]i in adult neurons, such as releasable internal stores or voltage-
dependent calcium channels, were not present at the critical period.
Instead, mechanisms that reduce free calcium, such as buffering and
pumping, were the most robust. When a large, focal calcium rise was
produced in an AP axon by making a lesion with a UV microbeam (leading to
eventual death of these neurons), calcium did not rise quickly throughout
the cell, but rather moved in a slow (0.05-0.25 micron/sec) wave front away
from the lesion site, into other processes of the damaged cell.
Furthermore, when a calcium wave front reached the growth cone of a
transient axon, it crossed at the gap junctions into the coupled axon of
the neighboring AP neuron, but went no further. Since it is known that an
AP responds to a neighbor's death by reinitiating growth only in that axon
that contacts the dying cell (Gao and Macagno, 1987b; Gao, 1989), these
observations are consistent with calcium playing a role in the signaling of
cell death to homologs that are coupled to a dying cell.
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