RT Journal Article
SR Electronic
T1 The Semaphorin Receptor PlexinA3 Mediates Neuronal Apoptosis during Dorsal Root Ganglia Development
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12427
OP 12432
DO 10.1523/JNEUROSCI.3573-08.2008
VO 28
IS 47
A1 Ben-Zvi, Ayal
A1 Manor, Osnat
A1 Schachner, Melitta
A1 Yaron, Avraham
A1 Tessier-Lavigne, Marc
A1 Behar, Oded
YR 2008
UL http://www.jneurosci.org/content/28/47/12427.abstract
AB Extensive neuronal cell death during development is believed to be due to a limiting supply of neurotrophic factors. In vitro studies suggest that axon guidance molecules directly regulate neuronal survival, raising the possibility that they play a direct role in neuronal cell death in vivo. However, guidance errors may also influence survival indirectly due to loss of target-derived neurotrophic support. The role of guidance molecules in neuronal death in vivo has thus been difficult to decipher. Semaphorin3A, a repulsive guidance cue for sensory neurons, can induce sensory neuron death in vitro. Null mice studies of the Semaphorin3A coreceptors showed that guidance activity is mediated by PlexinA4, but PlexinA3 partially compensates in PlexinA4−/− mice. Here we demonstrate that both Plexins contribute to Sema3A-induced cell death in vitro, albeit in a different hierarchy. PlexinA3 is absolutely required, while PlexinA4 makes a smaller contribution to cell death. We found that PlexinA3−/− mice, which, unlike PlexinA4−/− mice, do not exhibit sensory axon patterning defects, show reduced neuronal apoptosis and an increased number of DRG neurons. Semaphorin3A involvement in neuronal death in vivo was demonstrated by a sensitization experiment using the proapoptotic effector Bax. Our results identify Plexins as mediators of Semaphorin-induced cell death in vitro, and provide the first evidence implicating Semaphorin/Plexin signaling in neuronal survival independent of its role in axon guidance. The results also support the idea that naturally occurring neuronal cell death reflects not only competition for target-derived trophic factors, but also the action of proapoptotic signaling via a Semaphorin/Plexin pathway.