Blau, Axel et al. (2015) International Worm Meeting "Si elegans - A neuromimetic emulation platform for exploring C. elegans' neurobiology and behavior."

Ferrara, Lorenzo, Callaly, Frank, Morgan, Fearghal, Mc Ginley, Brian, Leskovsky, Peter, Blau, Axel, Machado, Pedro, Krewer, Finn, McGinnity, Martin, Epelde, Gorka, Petrushin, Alexey, Mujika, Andoni

[International Worm Meeting, 2015]

Despite being one of the five best-characterized model organisms, there is still only sparse knowledge on how C. elegans' nervous system codes for its rich behavioral repertoire. The European Si elegans project aims at unravelling C. elegans' nervous system function (hermaphrodite) by its emulation with 302 parallelly interconnected field-programmable gate array (FPGA) neurons and by embodying this hardware nervous system with a biophysically accurate soft-body representation in a virtual behavioral arena. We critically discuss past and present neurocomputational approaches and pitfalls of simulating nervous system function. We then present the first Si elegans implementation and system integration steps with focus on its key components and challenges. The biophysics-based simulation platform shall allow scientists to test neural processing hypotheses and (un)published behavioral paradigms. Users will have access to all currently known and biologically relevant variables for the reverse-engineering of nervous system function to confirm or even anticipate some of the underlying principles. This contribution aims at opening a scientific discourse on the requirements, possibilities and limits of the faithful biomimetic emulation of an organism from both the biological and engineering perspectives.Acknowledgements: This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement ndeg 601215, FET Proactive, call ICT-2011.9.11: Neuro-Bio-Inspired Systems (NBIS). www.si-elegans.eu.

Lung Yam et al. (2002) West Coast Worm Meeting "wly-1 mutations cause axonal degeneration"

Lung Yam, Scott G Clark, Catherine Chiu

[West Coast Worm Meeting, 2002]

Axons undergo a characteristic degeneration following axotomy (Wallerian degeneration) or in some neurodegenerative diseases (dying back degeneration). Raff, Whitmore and Finn have suggested that the elimination of axon branches during normal development might involve the same axonal degeneration mechanism, of which the molecular basis is poorly understood. Mutations in wly-1 (Wallerian-like decay) cause the distal half of the PVQ axons to degenerate. The PVQs are located in the tail and each extends a single axon that runs along the ventral nerve cord to the nerve ring. Using the sra-6::gfp reporter to visualize the PVQs, the PVQ axons extend to the nerve ring and appear normal in young wly-1 larvae, whereas these axons are truncated at various positions between the vulva and posterior bulb of the pharynx in L4 and older animals. Several GFP-labeled blobs are typically observed in the ventral nerve cord anterior to the PVQ axon stump, suggesting a catastrophic degeneration of the distal half of the PVQ axon. wly-1 double mutants with ced-3 or ced-4 mutations, which block programmed cell death, exhibit a similar PVQ axonal degeneration phenotype as wly-1 single mutants. The sisters of PVQ die during wildtype development; in these wly; ced double mutants, the zombie PVQ sisters exhibit a similar axonal degeneration phenotype as PVQ. To examine the PVQ axonal degeneration in greater detail, we are generating reagents to visualize axonal cytoskeletal structures as well as analyzing the time course of the decay. We are also investigating the relationship of the wly-1-induced degeneration to various axonal degeneration phenomena observed in vertebrates. We cloned wly-1 and found that it encodes a protein with no recognizable homologues in other organisms, aside from nematodes. Both wly-1 alleles are recessive, nonsense mutations, suggesting that they do not produce neurotoxic products per se. A wly-1::gfp transcriptional reporter is expressed broadly in muscle and neurons and a WLY-1-GFP translational fusion protein is detected in the cytoplasm of neurons when expressed under the wly-1 promoter. The wly-1 cDNA expressed under the sra-6 promoter, which drives expression in PVQ, ASH and ASI, completely rescued the axonal degeneration phenotype, suggesting that wly-1 functions cell autonomously. Although the sequence of wly-1 is presently unenlightening, the wly-1mutant should be useful in the investigation of axonal degeneration in C. elegans.

Lung Yam et al. (2003) International Worm Meeting "wly-1 mutations cause axonal degeneration"

Lung Yam, Catherine Chiu, Scott Clark

[International Worm Meeting, 2003]

Axons undergo a characteristic degeneration following axotomy (Wallerian degeneration) or in some neurodegenerative diseases ('dying back' degeneration). Raff, Whitmore and Finn have suggested that the elimination of axon branches during normal development might involve the same axonal degeneration mechanism. The molecular basis of these degenerative and developmental processes is poorly understood. wly-1 (Wallerian-like decay) mutations caused the distal half of the PVQ axons to degenerate. PVQ is located in the tail and each extends a single axon along the ventral nerve cord to the nerve ring. Using an sra-6::gfp reporter, we found that the PVQ axons appeared normal in wly-1 L1 larvae but developed swellings along the distal half in L2 and L3 animals. Most axons were truncated at various positions between the vulva and posterior bulb of the pharynx in L4 and older animals. Several GFP-labeled blobs were typically observed anterior to the axon stump, suggesting a catastrophic degeneration of the distal half of the axon over a 24-36 hour period. The distal half of the HSN axon also degenerated, whereas axons of many other neurons appeared unaffected. For both PVQ and HSN, the proximal halves of the axons remained intact. A wly-1 double mutant with a ced-3 or ced-4 mutation, which block all programmed cell deaths, exhibited a similar PVQ axonal degeneration phenotype as a wly-1 single mutant, indicating that the wly-1-induced axonal degeneration is independent of the apoptotic pathway. We cloned wly-1 and found that it encodes a novel protein. Both wly-1 alleles are recessive, nonsense mutations, suggesting that they do not produce neurotoxic products per se. A wly-1::gfp transcriptional reporter is expressed broadly in neurons and muscle and a WLY-1-GFP translational fusion protein is detected in the cytoplasm of neurons when expressed under the wly-1 promoter. The expression of WLY-1 under the sra-6 promoter, which drives expression in PVQ, ASH and ASI, completely rescued the PVQ axonal degeneration phenotype, indicating that wly-1 functions cell autonomously. We are currently investigating when wly-1 function is needed as well as searching for other molecules involved in wly-1-mediated axonal degeneration. wly-1 might function to protect the axon from cellular damage that would activate a degenerative process. Alternatively, wly-1 might function to regulate a degenerative process in response to cellular damage or developmental cues. In either case, wly-1 mutants should be useful in the study of axonal degeneration in C. elegans and vertebrates.