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The Journal of Neuroscience, August 1, 2002, 22(15):6659-6669
Nerve Growth Factor and Semaphorin 3A Signaling Pathways Interact
in Regulating Sensory Neuronal Growth Cone Motility
Vassil D.
Dontchev2 and
Paul C.
Letourneau1
1 Department of Neuroscience, University of Minnesota,
Minneapolis, Minnesota 55455, and 2 Department of Anatomy
and Histology, Medical University-Sofia, Sofia, 1431 Bulgaria
Neurotrophins and semaphorin 3A are present along pathways and in
targets of developing axons of dorsal root ganglion (DRG) sensory
neurons. Growth cones of sensory axons are probably regulated by
interaction of cytoplasmic signaling triggered coincidentally by both
types of guidance molecules. We investigated the in
vitro interactions of neurotrophins and semaphorin 3A (Sema3A)
in modulating growth cone behaviors of axons extended from DRGs of
embryonic day 7 chick embryos. Growth cones of DRGs raised in media
containing 10 9 M NGF or BDNF were
more resistant to Sema3A-induced growth cone collapse than when
DRGs were raised in 10 11 M NGF. After
overnight culture in 10 11 M NGF, a 1 hr treatment with 10 9 M NGF or BDNF
was sufficient to increase growth cone resistance to
Sema3A-induced collapse. This neurotrophin-mediated decrease in the
collapse response of DRG growth cones was not associated with reduced
expression on growth cones of the Sema3A-binding protein neuropilin-1.
A series of pharmacological studies followed. Phosphatidylinositol 3 kinase activity is not required for these effects of NGF. The
effects of inhibitors and activators of protein kinase A (PKA) indicate
that PKA activity is involved in NGF modulation of Sema3A-induced
growth cone collapse. The effects of inhibitors and activators of PKG
indicate that PKG activity is involved in Sema3A-induced growth cone
collapse. The effects of inhibitors also indicate that
Rho-kinase activity is involved in Sema3A-induced growth cone
collapse. These results are consistent with the idea that growth cone
responses to an individual guidance cue depend on coincident signaling
by other guidance cues and by other regulatory pathways.
Key words:
neurotrophin; semaphorin3A; protein kinase A; protein
kinase G; ROCK kinase; growth cone
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156659-11$05.00/0
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