person: Daniel Colon-Ramos

Marine Biological Laboratory; Woods Hole MA, United States of America; Whitman Center WormGUIDES.org Yale University Medical School; New Haven CT, United States of America University of Puerto Rico; San Juan PR, United States of America

paper:

Colon-Ramos, Daniel A. (2009) International Worm Meeting "MOLECULAR MECHANISMS ACTIVATED BY THE UNC-40/DCC RECEPTOR TO DIRECT SYNAPTIC TARGET SELECTION."

Colon-Ramos, Daniel A.

[International Worm Meeting, 2009]

Neural circuits are assembled through the coordinated innervation of pre- and postsynaptic partners. We recently showed that in C. elegans connectivity between two interneurons (AIY and RIA) is orchestrated by glial cells that express UNC-6 (netrin). In the postsynaptic neuron RIA, UNC-6/Netrin is detected by the Netrin receptor, UNC-40/DCC, which plays a conventional guidance role in directing outgrowth of the RIA process ventrally towards the glia. In the presynaptic neuron AIY, UNC-40/DCC plays an unexpected and previously uncharacterized role, cell-autonomously promoting the assembly of presynaptic terminals in the immediate vicinity of the glia. We now find that MIG-10/lamellopodin is required for the Netrin receptor, UNC-40/DCC, to direct presynaptic localization in the AIY interneuron. MIG-10/lamellopodin localizes to presynaptic sites in an UNC-40/DCC dependent manner. Moreover, MIG-10/lamellopodin is required for presynaptic localization in AIY, but is dispensable for UNC-40/DCC dependent guidance in RIA. These results indicate that UNC-40/DCC-mediated presynaptic localization is genetically separable from UNC-40''s guidance role, and suggest that UNC-40/DCC directs presynaptic localization through the MIG-10/lamellopodin pathway.

paper:

Colon-Ramos D (2013) J Cell Biol "Daniel Colon-Ramos: observing and making connections. Interview by Caitlin Sedwick."

Colon-Ramos D

[J Cell Biol, 2013]

paper:

Daniel A Colon-Ramos et al. (2005) International Worm Meeting "Synaptogenesis in AIY"

Kang Shen, Daniel A Colon-Ramos

[International Worm Meeting, 2005]

AIY, a primary interneuron in C. elegans, receives inputs from multiple sensory neurons to modulate behaviors such as thermotaxis, locomotion, chemotaxis and learning responses (1-5). Correct synaptic connectivity of AIY pre- and postsynaptic partners is critical for correct formation of the circuits which underlie these behaviors. Although the AIY processes contact multiple potential postsynaptic partners, AIYs form a stereotypical set of synapses with certain neurons at discreet areas of the axons (6). The molecular mechanisms used by AIY to discriminate between potential targets and form functional neuronal circuits are not understood. To understand synaptogenesis in AIY, we have developed a ttx-3::gfp::rab-3 marker which allows visualization of synaptic vesicle clusters in these neurons (Michael Nonet, personal communiation). The observed pattern of the vesicles clusters was consistent with the ultrastructural EM pattern reported for AIY presynaptic sites (6). Furthermore GFP::RAB-3 was absent from the AIY processes in unc-104 mutants, suggesting that the observed clusters are synaptic vesicles transported by the synaptic vesicle kinesin UNC-104 to the presynaptic sites. Interestingly we observed normal synaptic cluster pattern for AIY in syg-1(ky652), syg-2 (ky671) or syd-2 (ju37) mutants, suggesting that these molecules, important for synaptogenesis in other neurons, are not required for synaptogenesis in AIY. However, axon guidance molecules SAX-3 and UNC-6 were critical for normal synaptic cluster pattern, even when they did not severely disrupt axon guidance in AIY. We are currently carrying out genetic screens to better characterize how AIY finds its correct postsynaptic targets in the complex nerve ring environment. Bibliography1.I. Mori, Y. Ohshima, Nature 376, 344 (Jul 27, 1995). 2.M. Gomez et al., Neuron 30, 241 (Apr, 2001). 3.T. Ishihara et al., Cell 109, 639 (May 31, 2002). 4.J. M. Gray, J. J. Hill, C. I. Bargmann, Proc Natl Acad Sci U S A 102, 3184 (Mar 1, 2005). 5.E. L. Tsalik, O. Hobert, J Neurobiol 56, 178 (Aug, 2003). 6.J. G. White, E. Southgate, J. N. Thomson, S. Brenner, Philos Trans R Soc Lond B Biol Sci 275, 327 (Aug 10, 1976).

paper:

Daniel Colon-Ramos et al. (2007) International Worm Meeting "UNC-40/DCC specifies neural circuits by promoting local synaptogenesis."

Kang Shen, Daniel Colon-Ramos, Milica Margeta

[International Worm Meeting, 2007]

Neural circuits are assembled through the coordinated innervation of pre and postsynaptic partners, but how this process is orchestrated is not well understood. In the C. elegans nerve ring, interneurons AIY and RIA form synapses at a stereotyped location. Here we show that AIY-RIA connectivity is orchestrated by a pair of glial cells which secret UNC-6/Netrin. UNC-40/DCC plays a classic axon guidance role and directs the outgrowth of RIA processes towards the glia. Interesting, UNC-40/DCC also functions cell autonomously in AIY to promote local assembly of presynaptic terminals near the glial cell. Therefore, the glia cells function as guidepost for both axon guidance and synapse formation during the assembly of neural circuits in vivo.

paper:

Daniel Colon-Ramos et al. (2006) Neuronal Development, Synaptic Function, and Behavior Meeting "The immunoglobulin superfamily protein UNC-40 directs synaptic targeting in AIY"

Kang Shen, Daniel Colon-Ramos

[Neuronal Development, Synaptic Function, and Behavior Meeting, 2006]

The C. elegans nervous system develops in a stereotyped manner: neurons innervate specific targets and form precise circuits that underlie nematode behaviors. How synaptic targeting is specified, and how correct wiring of the nematode brain influences behavior is not well understood. We have studied the development of the synapses formed by AIY: a primary interneuron in the retrovesicular ganglion which forms stereotyped synaptic connections to modulate behaviors such as thermotaxis, chemotaxis and learning. To understand how AIY"s precise synaptic targeting is specified we isolated mutants with abnormal synaptic vesicle distribution. One of these mutants, wy81, encodes Immunoglobulin Superfamily protein UNC-40. UNC-40 is a transmembrane IgSf protein critical for correct axon guidance in C. elegans and other organisms. However, in unc-40 mutants the cell morphology, cell migration and axon guidance are wild type for AIY. Interestingly, unc-40 mutants display an abnormal distribution pattern in the synaptic vesicle and active zone clusters of AIY. Mosaic analysis showed that unc-40 acts cell autonomously in the presynaptic neuron AIY and localizes to presynaptic terminals. Additionally, UNC-40 is sufficient to cluster synaptic vesicles and active zone proteins, as forced mislocalization of UNC-40 due to overexpression drives ectopic presynaptic terminal formation at the location of mislocalized UNC-40. UNC-40 ligand, UNC-6, is required for accumulation of UNC-40 to the region of future synaptic assembly. This region of the AIY process is adjacent to the cephalic ventral sheath cells, known to express UNC-6 near the nerve ring neuropile. Structure-function analysis showed that the UNC-40 intracellular domain is required for correct localization and clustering of the UNC-40 to the future sites of synaptic assembly. Together our data suggest that UNC-40 specifies the localization of presynaptic specializations, possibly by inducing presynaptic assembly in AIY.

disease ontology: colon Kaposi sarcoma [DOID:6804]

A sarcoma of colon that is located_in the colon.

disease ontology: colon leiomyosarcoma [DOID:5259]

A leiomyosarcoma and sarcoma of colon that is located_in the colon.

disease ontology: colon sarcoma [DOID:5260]

A colon cancer that arises from transformed cells of mesenchymal origin and is located_in the colon.

disease ontology: colonic disease [DOID:5353]

A intestinal disease located in the colon.