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The Journal of Neuroscience, October 15, 2000, 20(20):7691-7697
Semaphorin 3A Is Required for Guidance of Olfactory Axons in
Mice
Gerald A.
Schwarting1, 2,
Christine
Kostek1,
Naira
Ahmad1,
Christian
Dibble1,
Laurent
Pays1, and
Andreas W.
Püschel3
1 The Shriver Center, Waltham, Massachusetts 02452, 2 Department of Cell Biology, University of Massachusetts
Medical School, Worcester, Massachusetts 01655, and
3 Molecular Genetics Laboratory, Department of
Neurochemistry, Max-Planck-Institut for Brain Research, D-60528
Frankfurt, Germany
Semaphorin 3A (Sema3A) is a membrane-associated secreted protein
that has chemorepulsive properties for neuropilin-1 (npn-1)- expressing axons. Although mice lacking the Sema3A protein
display skeletal abnormalities and heart defects, most axonal
projections in the CNS develop normally. We show here that Sema3A is
expressed in the lamina propria surrounding the olfactory epithelium
(OE) and by ensheathing cells in the nerve layer of the ventral
olfactory bulb (OB) throughout development. Subsets of sensory neurons
expressing npn-1 are distributed throughout the OE and extend fibers to
the developing OB. In wild-type mice, npn-1-positive
(npn-1+) axons extend to lateral targets in
the rostral OB and medial targets in the caudal OB,
avoiding regions expressing Sema3A. In Sema3A homozygous mutant mice,
many npn-1+ axons are misrouted into and
through the ventral nerve layer, beginning as early as
embryonic day 13 and continuing at least until birth. At
postnatal day 0, npn-1+ glomeruli are atypically
located in the ventral OB of Sema3A / mice,
indicating that aberrant axon trajectories are not corrected during
development and that connections are made in inappropriate target
regions. In addition, subsets of OCAM+ axons
that normally project to the ventrolateral OB and some lactosamine-containing glycan+ axons that normally
target the ventral OB are also misrouted in Sema3A mutants. These
observations indicate that Sema3A expression by ensheathing cells plays
an important role in guiding olfactory axons into specific compartments
of the OB.
Key words:
Sema3A; neuropilin-1; ensheathing cells; axon guidance; olfactory; pattern formation
Copyright © 2000 Society for Neuroscience 0270-6474/00/20207691-07$05.00/0
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