Vidal-Gadea, Andres G. et al. (2013) International Worm Meeting "Magnetotaxis in C. elegans."

Vidal-Gadea, Andres G., Pierce-Shimomura, Jonathan T., Ward, Kristi A.

[International Worm Meeting, 2013]

The magnetic field of the Earth provides an ancient and continuous source of directional information to organisms able to detect it. While the last half-century has seen the list of species capable of this feat grow steadily (from bacteria to mammals), the mechanisms by which magentosensation is accomplished in animals has remained elusive. Magnetotactic bacteria are known to harvest iron from their environment to build nanometer-sized "compasses" and evidence of magnetite has been reported in many magnetotactic animals. It remains unclear whether and how these putative "biological compasses" are used. This is partly due to the fact that a magnetosensory neuron has never been identified in any animal. We show that the nematode C. elegans readily orients to common magnets in addition to the Earth's magnetic field. Using a custom-built magnetic cage, we tested worms in magnetic fields controlled along three dimensions. Worms migrated at an angle to the field, in what would be the "down" direction. Our findings suggests that the Earth's magnetic field may serve as a better cue than gravity for these tiny animals to orient while burrowing. Through behavioral analysis of mutants as well as cell-specific rescue and ablation, we next identified a pair of amphid sensory neurons as necessary and sufficient to mediate magnetotaxis in C. elegans. Functional calcium imaging performed on these neurons revealed calcium transients induced by magnetic fields. Genes and neurons required for magnetotaxis are distinct from those previously reported to be essential for electrotaxis. Magnetic orientation in C. elegans appears to take place through a light-independent mechanism, and to rely on a cGMP-dependent transduction pathway. To our knowledge, this represents the first report of sensory neurons required for magnetic orientation in any species.

Vidal-Gadea, Andres et al. (2015) International Worm Meeting "Burrowing behavior of C. elegans used to study neuromuscular disorder models."

Vidal-Gadea, Andres, Parikh, Adhishri, Pierce-Shimomura, Jonathan, Cohn, Jesse, Hwang, Grace, Beron, Celia

[International Worm Meeting, 2015]

The nematode Caenorhabditis elegans is a powerful model system for the study of human neuromuscular function and disorders. However, many worm models of human disease only show mild crawling phenotypes. In their natural habitat, C. elegans likely spends much of the time burrowing through the soil matrix. We developed a burrowing assay to challenge motor output by placing worms in agar-filled pipettes of increasing densities. We find that burrowing involves distinct kinematics and turning strategies from crawling that vary with the properties of the substrate. We show that Duchenne muscular dystrophy model (dys-1) mutants crawl normally but are severely impaired in burrowing. In stark contrast with wild-type, muscular degeneration in the dys-1 mutant is hastened and exacerbated by burrowing. We performed a genetic screen and isolated several suppressor mutants with proficient burrowing in a dys-1 mutant background. Further study of burrowing in C. elegans will enhance the study of diseases affecting neuromuscular integrity, and provide insights into the natural behavior of this and other nematodes.

Vidal-Gadea, A.G. et al. (2019) International Worm Meeting "Development of a novel assay to identify genes involved in host infection by parasitic nematodes."

Risi, G., Salinas, G, Vidal-Gadea, A.G.

[International Worm Meeting, 2019]

Helminths are parasitic worms that present major challenges to human health, infecting about a quarter of the world's population. They also affect the health and productivity of farm livestock (especially sheep) as well as crops. Unfortunately, there is an increasing development of heminths' resistance against the currently veterinary used anthelmintics and concern is growing that resistance may arise in humans parasitic nematodes. In order to get to their target organs, parasitic worms have to cross biological barriers. If unable to do so, they will not be able to properly develop, have offspring, and complete their life cycles. We developed an automatic burrowing assay that allows us to use the nematode C. elegans to screen for molecular targets and compounds that may be used to interfere with the ability of parasitic helminths to cross biological barriers (and completing their life cycles). We conducted an RNAi screen targeting C. elegans genes present in parasitic helminths but not present in vertebrates. We found that about 7% of the genes tested significantly impaired burrowing performance in C. elegans. Of these, about 80% were neuronal genes which we are now working to validate on parasitic species. C. elegans experimental amenability and behavioral repertoire provide rich substrates for the identification of antihelminthic targets.

Vidal-Gadea, Andres et al. (2015) International Worm Meeting "Geographical tuning in magnetotactic response across C. elegans wild-type isolates."

Ward, Kristi, Beron, Celia, Vidal-Gadea, Andres, Pierce-Shimomura, Jonathan

[International Worm Meeting, 2015]

Rotation of the earth's liquid core generates a magnetic field used by many organisms to navigate their environment. While some animals such as turtles and birds use the magnetic field to engage in horizontal migrations, other organisms like magnetotactic bacteria use it to guide their migrations vertically. We find that C. elegans readily orients to artificial magnetic fields of earth strength. When assaying responses to the natural magnetic field of the earth, we found that worms appear to use the geomagnetic field to guide vertical migrations via an identified a pair of sensory neurons. Because the orientation of the geomagnetic field differs across the globe, we tested the magnetotactic ability and migratory preference of the standard lab strain (N2), and of wild-type strains isolated from different locations across the planet. We found that different populations displayed an innate preference to migrate at an angle to magnetic fields of earth-strength that would optimize their UP or DOWN direction when burrowing in their native global location. For instance, in England the geomagnetic field pierces the earth at +66 degrees (north points down). We found that well-fed British N2 worms prefer to migrate 120 degrees to an earth-strength artificial magnetic field. This seemingly arbitrary angle corresponds to the optimal angle to orient them upward when burrowing in England. By contrast, starved N2 worms migrated in the opposite direction (i.e. 300 degrees to the field), which would orient them downward in England. Consistent with natural populations adapting to local magnetic fields, we next found that worms isolated from Australia, where the geomagnetic field emanates out of the earth at -66 degrees (north points up), displayed an opposite innate pattern of migratory preference. Similar results were found for wild-type worms from Hawaii. This pattern of optimal natural variation in magnetic orientation in C. elegans serves as an excellent example to relate spatiotemporal genetic variation with a behavioral trait. The breath in number and distribution of wild-type C. elegans populations makes this a promising model for studying the effects of natural and artificial magnetic field variation on the behavior of a genetically tractable animal.

Vidal-Gadea A G et al. (2010) Neuronal Development, Synaptic Function and Behavior, Madison, WI "Biogenic amines mediate transition between crawling and swimming in C. elegans"

Brauner M, Gottschalk A, Erbguth K, Kressin L, Vidal-Gadea A G, Topper S, Young L, Pierce-Shimomura J T

[Neuronal Development, Synaptic Function and Behavior, Madison, WI, 2010]

A wide variety of animals must quickly adjust their pattern of locomotion to successfully navigate through different environmental niches. Selection and execution of the appropriate locomotory pattern is therefore paramount to survival. Although C. elegans is capable of performing many adaptive behaviors, it has been controversial whether forward crawling and swimming represent distinct gait-like forms of locomotion or the modulation of a single form of locomotion [1-3]. Biogenic amines have been shown to mediate the transition between gait-like forms of locomotion across taxa as diverse as sea slugs, leeches, lampreys and humans. We previously reported that C. elegans crawls and swims with distinct kinematics and different patterns of muscle activity [2]. We now combine quantitative behavioral analysis, optogenetic tools and neuronal ablation to show that C. elegans uses biogenic amines to switch between crawling and swimming in a gait-like manner. As in other invertebrates, we find that serotonin mediates the smooth transition from crawling to swimming in C. elegans. Serotonin is further required to inhibit motor behaviors (e.g. foraging and pharyngeal pumping) during swimming that normally only accompany crawling. Mirroring the role of dopamine in other invertebrates, C. elegans uses dopamine to successfully initiate and maintain crawling when emerging from liquid. Over 600 million years of separate evolution notwithstanding, the highly conserved role played by biogenic amines such as dopamine and serotonin across taxa attests to how vital their function is to adaptive strategies for locomotion. Korta J, Clark DA, Gabel CV, Mahadevan L, Samuel AD. J. Exp. Bio. 2007 210:2383-9.Pierce-Shimomura JT, Chen BL, Mun JJ, Ho R, Sarkis R, McIntire SL. PNAS. 2008 105:20982-7.Berri S, Boyle JH, Tassieri M, Hope IA, Cohen N. HSFP J. 2009 3:186-93.

Vidal-Gadea, Andres G et al. (2011) International Worm Meeting "C. elegans selects distinct crawling and swimming gaits via dopamine and serotonin."

Elbel, Erin, Axelrod, Abram, Erbguth, Karen, Topper, Stephen, Brauner, Martin, Vidal-Gadea, Andres G, Crisp, Ashley, Pierce-Shimomura, Jonathan, Young, Layla, Siegel, Dionicio, Maples, Thomas, Kressin, Leah, Gottschalk, Alexander

[International Worm Meeting, 2011]

The ability to select and switch between alternate locomotory gaits is shared among many animals that are required to transition between different environments. Failure to achieve motor transitions is often devastating to the organism as exemplified by patients with advanced Parkinson's disease. The nematode C. elegans is well adapted for locomotion on land and in water and is likely required to transition between these sub-niches in nature. Despite recent advances, it remains controversial if swimming and crawling are distinct gaits in C. elegans, and if so, how transitions between them are accomplished (1-4). Answering these questions could enable the use of this powerful model system to study the mechanisms underlying locomotory transitions. We used a multifaceted approach spanning in depth behavioral assays, mechanic and optogenetic stimulation, laser ablations, mutant analysis, and in vivo photolysis of caged amines to test whether the worm uses distinct gaits and to determine how they transition between them. We show through a series of behavioral assays that in C. elegans crawling and swimming are distinct gaits. Dopamine released by ADE and PDE neurons is necessary and sufficient to initiate and maintain crawling by a pathway activating D1-like receptors. Conversely, serotonin is necessary and sufficient to initiate and maintain transition from crawling to swimming and to inhibit a set of crawl-specific behaviors. We found these transitions to be modulated by the balance between dopamine and serotonin. These amines have been found to play crucial roles in transition between alternate locomotory forms in diverse species stressing the importance locomotor transitions have for survival. Further study of locomotory switching in C. elegans and its dependence on dopamine may provide insight into comparable motor deficits observed in Parkinson's disease. 1) Boyle H et al. N. Front. Behav. Neurosci. 2011 5:10 doi: 10.3389/fnbeh.2011.00010. 2) Mesce KA, Pierce-Shimomura JT. Front. Behav. Neurosci. 2010 4:49 doi: 10.3389/fnbeh.2010.0004 3) Vidal-Gadea AG et al. 2009 Neuroscience 366:17 Calabrese R: Faculty of 1000 Biology, 11 November, 2009. Conference 2009 October 16-21. Available at: http://f1000biology.com/ article/id/1182956/evaluation 4) Fang-Yen C et al. 2010 PNAS 107, 20323-20328.

Moon, K. et al. (2019) International Worm Meeting "Gait selection of Caenorhabditis elegans is regulated by mechanosensitive DEG/ENaC channels."

Moon, K., Kim, K., Kim, J., Yeon, J.

[International Worm Meeting, 2019]

Animals change their locomotion or gaits in response to environmental condition. In vertebrates, gait transition has been shown to be mediated by monoamines, which is conserved across many species including the nematode Caenorhabditis elegans (Vidal-Gadea et al., 2011). However, molecular mechanisms of gait transition are still unclear. C. elegans exhibits two gaits, swimming in liquids and crawling on dense gels. C. elegans genome contains evolutionarily conserved 28 DEG/ENaC channels, of which functions may be involved in mechanosensory transduction and locomotion (Goodman and Schwarz, 2003). We first hypothesized that mechanosensitive channels could act as a gait transition initiator and examined crawl-to-swim transition phenotype in DEG/ENaC mutants. We found that while acd-5 mutants show normal crawling, transition from crawling to swimming upon liquid exposure is defective, suggesting roles of ACD-5 in gait transition. We are currently generating acd-5 rescue lines and examining expression pattern of acd-5.

Topper, Stephen M. et al. (2013) International Worm Meeting "Dopaminergic control of gait switching in C. elegans."

Pierce-Shimomura, Jonathan, Aguilar, Sara, Topper, Stephen M., Young, Layla

[International Worm Meeting, 2013]

The ability to switch between different forms of locomotion is critical to many aspects of survival, whether it is switching from walking to running to evade predators, or switching to a slower gait to obtain food. However, the neuronal mechanisms of gait switching are not well understood. We recently showed C. elegans, displays distinct crawl and swim gaits, mediated by dopamine and serotonin, respectively (Vidal-Gadea et al., 2011). Further investigation into the role of dopamine signaling in the transition to crawl has indicated the D1-like dopamine receptor dop-4 as a key component. Laser microablation of dop-4-expressing neurons has revealed single neurons that are required for the transition to crawl. Optogenetic activation of dop-4-expressing neurons via the light-activated GPCR optoXRB2 induces crawl-like behavior in swimming worms. Finally, expression of dop-4 in specific subsets of dop-4 neurons is sufficient to rescue the swim to crawl transition. We are now combining noninvasive imaging of these neurons in freely moving worms with optogenetics to dissect how dopamine controls gait switching at the circuit level. A genetic analysis dopaminergic locomotory in C. elegans may reveal fundamental principles on gait switching with implications for many fields, including the study of human ailments such as Parkinson's disease.

Bainbridge, C. et al. (2019) International Worm Meeting "Investigating the role of mechanoreceptors for magnetotransduction in C. elegans."

Leonard, N., Bainbridge, C., Owoyemi, T., Owoyemi, K., Vidal-Gadea , A., Paluzzi, B.

[International Worm Meeting, 2019]

Many organisms, from bacteria to mammals, rely on magnetic fields to orient within their environment and perform impressive feats of navigation. Despite the prevalence of magnetic orientation across taxa, mechanisms for magnetoreception remain poorly understood. A favored model for magnetoreception proposes coupling of magnetic particles or proteins to mechanical-force sensitive channels (mechanoreceptors). Mechanoreceptors are thought to transduce the mechanical forces of particle alignment with magnetic fields into electrical signals for sensory cells. Mechanoreceptors are functionally versatile and recruited to transduce diverse sensory modalities, making them promising candidates for magnetoreceptors. We previously found that C. elegans detects and orients to magnetic fields with a pair of magnetosensory neurons (AFDs). C. elegans has about 50 described mechanoreceptors. We are using the nematode C. elegans to test the potential role of mechanoreceptors in magnetic field transduction. To approach this question, I will use a combination of RNA interference to silence mechanoreceptor expression and automated machine vision to assess mechanoreceptor necessity for magnetic orientation. To support their role as potential magnetoreceptors, mechanoreceptors will be fluorescently labelled to determine their proximity to AFD neurons. Our results have the potential to identify the first working magnetoreceptor system in any animal.

Topper, S. et al. (2011) International Worm Meeting "Role of dopamine in locomotory transitions in C. elegans."

Gottschalk, A., Young, L., Topper, S., Pierce-Shimomura, J., Vidal-Gadea, A.

[International Worm Meeting, 2011]

Many animals switch behavioral and locomotory patterns in order to move efficiently in different environments. We have found that the nematode C. elegans displays alternate forms of locomotion; crawling on firm substrates and swimming in liquid environments. These forms of motion appear to represent gaits because when we constrain worm speed with viscous solutions, worms swim at low viscosity, crawl at high viscosity and switch between crawling and swimming at intermediate viscosity. Neuromodulators such as dopamine have conserved roles in switching between locomotory forms as evident in human Parkinson's disease patients who have trouble initiating voluntary motor commands. We investigated a role for dopamine in C. elegans locomotory transitions. Ablation of dopamine neurons, reduced dopamine synthesis, or deletion of the D1-like dopamine receptors (dop-1 or dop-4) impaired the transition from swim to crawl, but not crawl to swim. Furthermore, photoactivation of channelrhodopsin2 in the dopamine neurons was sufficient to induce crawl-like behavior in the swimming animal. Loss of the dop-1 receptor significantly reduced the amount of crawl-like behavior after photoactivation of dopamine neurons, while loss of dop-4 entirely eliminated photo-induced crawl-like behavior . Further investigation into dop-4 will elucidate downstream components that have a role in the swim to crawl transition.