Worm Breeder's Gazette 14(4): 77 (October 1, 1996)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Department of Pathology Robert Wood Johnson Medical School Piscataway, NJ 08854
We have examined the role of UNC-6 in nervous system development
using the SDQR and surrounding neurons. The SDQR is a particularly good
marker to study the effects of proposed UNC-6 gradients because it is
born late and its axon migrates late in the first larval stage, well
after initial UNC-6 expression. The SDQR axon first migrates dorsally
from its cell body at the ALMR tract to the dorsal sublateral nerve,
where it turns and travels anteriorly. Growth cone guidance is often
describe as an attraction or repulsion. For the SDQR a simple model
would be that the growth cone is initially repelled dorsally by the
increasing dorsal to ventral gradient of UNC-6 which was produced
earlier by ventral epidermoblast cells. Upon reaching the sublateral
nerve the axon fasciculates and is guided anteriorly by cues along the
nerve.
We have observed SDQR axon migrations in wild type, unc-6 null
mutants, and in different strains where UNC-6 is ectopically expressed
to study how the growth cone responds to guidance cues in vivo. The
experiments show that the SDQR growth cone does not require a nerve
tract to turn anteriorly, can be redirected by ectopic UNC-6, and can
migrate towards or away from an UNC-6 source.
From the migrational patterns which are observed it is difficult
to explain the circumferential to longitudinal SDQR growth cone
migration in terms of requiring fasciculation along an established
nerve, encountering new guidance cues, or expressing new receptors en
route. We propose that directional information for the migrating SDQR
growth cone is derived from the concurrent interpretation of
dorsoventral and anteroposterior cues. Migrations in unc-6 (-) animals
show that opposing an UNC-6 mediated response are the influences of
another cue(s) that mediates a ventral response. According to our
model, during the initial SDQR circumferential migration, the cell!s
navigational program induces a greater response to the UNC-6 dorsal cue
and a balanced response to anterior and posterior cues. The SDQR growth
cone migrates circumferentially until the dorsal and ventral mediated
responses are balanced due to the changing concentrations of
extracellular dorsal and ventral cue ligands. At the same time this
change influences the response to anteroposterior cues. We suspect that
the dorsal signal (UNC-6) favors a response towards posterior migrations
and the ventral signal towards anterior migrations so that at the dorsal
sublateral region the signal for an anterior directed migration
predominates. In support of this notion, circumferential growth cone
migrations of animals in the unc-6 (-) background are ventrally
directed and will always turn anteriorly (never posteriorly) at
incorrect dorsoventral locations. However, in the ectopic UNC-6
expressing animals where the growth cone may experience levels of UNC-6
that are higher than in wild type animals, there are dorsally oblique
and sometimes short posterior migrations. SDQR is not driven to the
dorsal cord by ectopic UNC-6, but instead is driven anteriorly at the
dorsal sublateral region (even when the dorsal sublateral nerve is
missing), presumably this is a response to the increasing ventral cue
levels. Finally, coupled and competing responses may explain why in
some cases SDQR can paradoxically migrate towards an UNC-6 source.
In brief, the pathway of the SDQR growth cone may be determined
by the initial expression of receptors. These receptors subsequently
mediate responses that orient the growth cone relative to the pattern of
extracellular guidance cues. Because direction information is
integrated, the SDQR is directed along a multi-directional route. As
opposed to relying on new directional instructions during its migration,
the SDQR can determine its position relative to the extracellular cues
like a traveler determining position to the points of a compass.
Together a system of temporally and spatially regulated patterns of
guidance cues and growth cones that orient relative to the patterns,
suggests a general mechanism by which axons may be positioned during
embryonic scaffold formation.