Worm Breeder's Gazette 14(4): 76 (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.

UNC-6 and the dorsoventral positioning of cells and nerves

Xing-Cong Ren, Eileen Ruppert, William G. Wadsworth

Department of Pathology Robert Wood Johnson Medical School Piscataway, NJ 08854

        During embryogenesis,  the basic axon scaffold of the nervous
system is formed by special axons that pioneer pathways between groups
of cells.   To find  their way, the pioneer growth cones detect specific
cues in their extracellular environment.  One of these guidance cues is
netrin.  Observations and experimental manipulations in vertebrates and
nematodes have shown that netrin is a bifunctional guidance cue that can
simultaneously attract and repel axons  (Hedgecock et al., 1990; Ishii
et al., 1992; Kennedy et al., 1994; Serafini et al., 1994).  During the
formation of the basic axon scaffold in C. elegans,  the netrin UNC-6 is
expressed by neuroglia and pioneer neurons to provide hierarchical
guidance cues throughout the animal  (Wadsworth et al., 1996; Wadsworth
and Hedgecock, 1996).   Each cue has a characteristic role depending on
the cell type, its position, and the developmental stage.  These roles
include activities as global,  decussation, and labeled-pathway cues.
This hierarchical model of UNC-6 netrin mediated guidance suggests a
method by which guidance cues can direct formation of basic axon
scaffolds in developing nervous systems.

        To further study development of the embryonic axon scaffold, we
have ectopically expressed UNC-6,  laser ablated specific
UNC-6-expressing cells, and studied nerve development in unc-6  mutants.
For the  laser ablation experiments we removed the midline PVT neuron
that expresses UNC-6 during embryogenesis and which is thought to direct
pioneer axons for ventral nerve cord/ lumbar commissure development.  In
these animals, the commissures do not form, instead multiple axon tracts
develop, often with misguided trajectories to the ventral nerve cord.
We have  also examined the migrations of GFP-labeled axons and cells in
unc-6  null mutants.  Many, but not all, longitudinally migrating axonal
growth cones stray dorsally and ventrally in the animals.  For the
ectopic expression studies, heterologous promoter sequences from the
mec-7 and unc-119 genes (provided by A. Fire and D. Pilgrim (Maduro and
Pilgrim, 1995)) were linked to full-length unc-6   genomic DNA,
integrated transgenic lines were established in various genetic
backgrounds, and the migrations of axons were scored in each strain.  In
these animals the patterning of nerve tracts is altered near neurons
that ectopically express UNC-6.

        We conclude from these experiments that a global UNC-6 netrin
cue has a broad role in positioning cells and longitudinal nerves along
the dorsoventral axis. Furthermore, that spatial UNC-6 gradients can be
formed in vivo  and that these UNC-6 gradients can direct axon
migrations.   The hierarchical model predicts that UNC-6 expression by
special neurons alters a global UNC-6 pattern to direct migrations at
specific locations and we believe the current experiments help to
demonstrate this ability.

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