RT Journal Article SR Electronic T1 Serotonergic Neurosecretory Synapse Targeting Is Controlled by Netrin-Releasing Guidepost Neurons in Caenorhabditis elegans JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1366 OP 1376 DO 10.1523/JNEUROSCI.3471-12.2012 VO 33 IS 4 A1 Jessica C. Nelson A1 Daniel A. Colón-Ramos YR 2013 UL http://www.jneurosci.org/content/33/4/1366.abstract AB Neurosecretory release sites lack distinct postsynaptic partners, yet target to specific circuits. This targeting specificity regulates local release of neurotransmitters and modulation of adjacent circuits. How neurosecretory release sites target to specific regions is not understood. Here we identify a molecular mechanism that governs the spatial specificity of extrasynaptic neurosecretory terminal (ENT) formation in the serotonergic neurosecretory–motor (NSM) neurons of Caenorhabditis elegans. We show that postembryonic arborization and neurosecretory terminal targeting of the C. elegans NSM neuron is dependent on the Netrin receptor UNC-40/DCC. We observe that UNC-40 localizes to specific neurosecretory terminals at the time of axon arbor formation. This localization is dependent on UNC-6/Netrin, which is expressed by nerve ring neurons that act as guideposts to instruct local arbor and release site formation. We find that both UNC-34/Enabled and MIG-10/Lamellipodin are required downstream of UNC-40 to link the sites of ENT formation to nascent axon arbor extensions. Our findings provide a molecular link between release site development and axon arborization and introduce a novel mechanism that governs the spatial specificity of serotonergic ENTs in vivo.