Glia Promote Local Synaptogenesis Through UNC-6 (Netrin) Signaling in C. elegans

Abstract

Neural circuits are assembled through the coordinated innervation of pre- and postsynaptic partners. We show that connectivity between two interneurons, AIY and RIA, in Caenorhabditis elegans is orchestrated by a pair of glial cells that express UNC-6 (netrin). In the postsynaptic neuron RIA, the netrin receptor UNC-40 (DCC, deleted in colorectal cancer) plays a conventional guidance role, directing outgrowth of the RIA process ventrally toward the glia. In the presynaptic neuron AIY, UNC-40 (DCC) plays an unexpected and previously uncharacterized role: It cell-autonomously promotes assembly of presynaptic terminals in the immediate vicinity of the glial cell endfeet. These results indicate that netrin can be used both for guidance and local synaptogenesis and suggest that glial cells can function as guideposts during the assembly of neural circuits in vivo.

Amphetamine in Adolescence Disrupts the Development of Medial Prefrontal Cortex Dopamine Connectivity in a dcc-Dependent Manner

“…1997; Winberg et al, 1998;Dent et al, 2004;Colón-Ramos et al, 2007;Manitt et al, 2009). Compromised DCC signaling induced by amphetamine during adolescence, a period of intense mPFC synaptic refinement, may therefore lead to the decrease of dopamine presynaptic sites by disrupting these post-axonal pathfinding events.…”

Regulation of dendritic development by semaphorin 3A through novel intracellular remote signaling

“…In this situation, UNC-6 may act as a short-range signaling molecule, creating microenvironments that promote synaptogenesis. 2 In either case, specific sets of proteins control synaptogenesis through mechanisms that require local cell-cell contact. In addition to neuronal wiring, axon guidance molecules and their receptors preset at synapses in the adult nervous system also influence synaptic plasticity in learning and memory.…”

The dual role of the ligand UNC-6/Netrin in both axon guidance and synaptogenesis inC. elegans

“…4 They were found mainly in the "elbow" region ( Fig. 1, zone 2) and about eight more complex-containing areas were found in the region most distant from the cell body within the nerve ring in wild-type animals ( Fig.…”

“…UNC-40/DCC/Fra plays two independent roles in establishing the connection between the pre-synaptic AIY amphid inter-neuron and its postsynaptic partner, the RIA inter-neuron in the nerve ring of C. elegans, since it is involved in both axon guidance of RIA and synapse localization in AIY. 4 The two neurons are located in the head region, close to the nerve ring and can be visualized using cell-specific markers (Fig. 1).…”

“…One notable aspect of this process is that the glialsecreted cue is a well-known axon guidance molecule, namely Netrin/UNC-6, but here it plays an additional and surprising role in selecting the site for the construction of a pre-synaptic complex. 4 UNC-6/Netrin, is a well-known bi-functional axon guidance cue that can attract some axons and repel others. It is a laminin-related molecule, originally isolated from C. elegans, with homologues in higher organisms.…”