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J Neurosci 2009 Sep 09;2936:11065-77. doi: 10.1523/JNEUROSCI.0947-09.2009.
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Netrin participates in the development of retinotectal synaptic connectivity by modulating axon arborization and synapse formation in the developing brain.

Manitt C , Nikolakopoulou AM , Almario DR , Nguyen SA , Cohen-Cory S .

Netrin has been implicated in retinal ganglion cell (RGC) axon pathfinding in a number of species. In Xenopus laevis, RGC axons reaching their target in the optic tectum can be repelled by a netrin-1 gradient in vitro, suggesting that netrin may also function in wiring events that follow successful axon pathfinding. Here, we examined the contribution of netrin to RGC axon arborization and synapse formation at the target. Time-lapse confocal microscopy imaging of individual RGC axons coexpressing GFP-synaptobrevin and DsRed in the intact Xenopus brain demonstrated a role for deleted in colorectal cancer (DCC)-mediated netrin signaling. Microinjection of netrin-1 into the tectum induced a rapid and transient increase in presynaptic site addition that resulted in higher presynaptic site density over a 24 h observation period. Moreover, netrin induced dynamic axon branching, increasing branch addition and retraction; a behavior that ultimately increased total branch number. In contrast, microinjection of DCC function-blocking antibodies prevented the increase in presynaptic site number normally observed in control axons as well as the associated increase in branch number and axon arbor growth. Dynamic analysis of axon arbors demonstrated that the effects of anti-DCC on axon morphology and presynaptic connectivity were attributable to a specific decrease in new synapse and branch additions, without affecting the stability of existing synapses and branches. Together, these results indicate that, in the absence of DCC signaling, RGC axons fail to branch and differentiate, and support a novel role for netrin in later phases of retinotectal development.

PubMed ID: 19741113
PMC ID: PMC2775133
Article link: J Neurosci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: dcc map2 ntn1 psd vamp1
Antibodies: Dcc Ab1 Dcc Ab2 Dlg4 Ab1 Neuronal Ab4 Ntn1 Ab1

Article Images: [+] show captions
References [+] :
Alsina, Visualizing synapse formation in arborizing optic axons in vivo: dynamics and modulation by BDNF. 2001, Pubmed, Xenbase