Vancoppenolle B et al. (1996) European Worm Meeting "Comparison of the early embryonic cell lineage of Caenorhabdi- tis elegans and Pellioditis marina, two rhabditid nematodes."

Vancoppenolle B, Coomans AV, Schnabel R, Borgonie G

[European Worm Meeting, 1996]

The early embryonic cell lineage of Pellioditis marina, a marine rhabditid with relatively short developing time was traced using a 4D-microscope. Although the general pattern of cell divisions is congruent with the lineage described for Caenorhabditis elegans by Sulston and coworkers, striking differences can be observed concerning migrations, timing of divisions and cell deaths. The AB, MS and C lineage of P. marina differ from those of C. elegans both in the occurence of additional cell deaths as wel as in the abscence of certain cell deaths. Additionaly, Caap does not divide in accordance with the characteristic period of the rest of the C lineage. In contrast with C. elegans, the E founder cell in P. marina undergoes a migration before gastrulation and devides into Ea and Ep only after E has entered the interior of the embryo. D and P4 divide in a similar way as in C. elegans.

Vancoppenolle B et al. (1997) International C. elegans Meeting "COMPARISON OF THE EMBRYONIC CELL LINEAGE OF CAENORHABDITIS ELEGANS AND PELLIODITIS MARINA"

Borgonie G, Vancoppenolle B, Schnabel R, Coomans AV

[International C. elegans Meeting, 1997]

The early embryonic cell lineage of Pellioditis marina, a marine rhabditid with relatively short developing time (9hrs at 25!C) was traced using a 4D-microscope. Although the general pattern of cell division is congruent with the lineage described for Caenorhabditis elegans by Sulston and Co-workers, striking differences can be observed concerning migrations, timing of divisions and cell deaths. The AB, MS and C lineage of Pellioditis marina differ from those of Caenorhabditis elegans both in the occurence of additional cell deaths as well as in the abscence of certain cell deaths. Additionaly, Caap does not divide in accordance with the characteristic period for the rest of the C-lineage. In contrast with Caenorhabditis elegans, the E founder cell in Pellioditis marina undergoes a migration before gastrulation and divides into Ea and Ep only after E has entered the interior of the embryo. D and P4 divide in a similar way as in Caenorhabditis elegans.

W Houthoofd et al. (2002) European Worm Meeting "Embryonic development of the free-living, marine nematode Pellioditis marina"

G Borgonie, A Coomans, B Vancoppenolle, K Jacobsen, W Houthoofd

[European Worm Meeting, 2002]

Until now only the embryonic cell lineage of the model organism Caenorhabditis elegans has been described (Sulston et al., 1983). The embryonic cell lineage of the free-living nematode Pellioditis marina has been traced from zygote up until the initiation of muscle contraction by means of 4D-microscopy, marking the second detailed description of the embryonic development of a nematode. P. marina is a close relative of C. elegans, but has adapted to a marine, brackish environment. The overall lineage resembles strongly on that of C. elegans, with a few small differences. The developmental tempo of the early embryogenesis (until division of E cell) is more then two times slower than C. elegans. But the primordial germline cell P4 is already present at the 15-cell stage (in C. elegans at the 24-cell stage). At the stage of muscle contraction (when most cells are established), P. marina has as many cells as C. elegans (571 cells) but less cell deaths (67 and 106 respectively). Tissue conservation varies from highly conserved to highly variable. The intestine, the primordial gonad and the body muscles are highly conserved in the two species, while the pharynx, the epidermis and the nervous system have a more variable configuration. The systematic position of Pellioditis remains unsolved, whether Caenorhabditis or Rhabditis is the closest relative. The early embryogenesis and the developmental timing are comparable with that of other Rhabditis species, while the overall cell lineage is almost identical with that of C. elegans. The latter is a strong argument to place P. marina close to C. elegans in the classification. In more primitive nematodes (like Halicephalobus sp.), sublineages form identical cells, which migrate to their exact location. C. elegans has adjusted these lineages to avoid these migrations (Borgonie et al., 2000). This could explain the chaotic' fate topology in the C. elegans cell lineage. P. marina falls in between: it has already adjusted the Caa-lineage to form two nerve cells, but still has migrations that are avoided in C. elegans.

Teixeira-Castro A et al. (2015) Brain "Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease."

Bessa C, Duarte-Silva S, Maciel P, Bessa J, Silverman RB, Miranda A, Kang S, Summavielle T, Oliveira S, da Silva Santos L, Neto MF, Esteves S, Brielmann RM, Neves-Carvalho A, Teixeira-Castro A, Oliveira P, Morimoto RI, Silva-Fernandes A, Jalles A

[Brain, 2015]

Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease.

Marafiga Cordeiro, Larissa et al. (2021) International Worm Meeting "Neuroprotective effects of rutin on ASH neurons in Caenorhabditis elegans model of Huntington's disease"

Franzen da Silva, Aline, Valandro Soares, Marcell, Antunes Soares, Felix, Arantes, Leticia, Obetine, Fabiane, Lopes Machado, Marina, da Silveira, Tassia, Marafiga Cordeiro, Larissa

[International Worm Meeting, 2021]

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disease. It occurs due to a mutation in the huntingtin gene with an abnormal CAG repeat, leading to a variable length N-terminal polyglutamine chain (poly-Q) which confers toxic functions to mutant Htt leading to neurodegeneration. Rutin is a flavonoid found in plants, buckwheat, some teas and also in apples. Although our previous studies have already indicated that rutin has protective effects in HD's models, more studies are needed to unravel its effects on protein homeostasis and the underlying mechanisms. In our study, we investigated the effects of chronic treatment with rutin in Caenorhabditis elegans model of HD focusing on ASH neurons and antioxidant defense. The synchronized L1 worms were placed on rutin-NGM plates and kept at 20°C. Rutin was added every 24 hours at concentrations of 15, 30, 60 and 120 muM. We assessed octanol response, neuronal polyQ aggregates and dye filling assay. In addition, we analyzed the downstream heat-shock protein-16.2 (HSP-16.2) and superoxide dismutase-3 (SOD-3). Overall, our data demonstrate that chronic rutin treatment maintains the function of ASH neurons in addition to decrease the degeneration of their sensory terminations. The mechanism proposed is antioxidant activity, through the overexpression of antioxidant enzymes and chaperones regulating proteostasis. Our findings provide new evidences about rutin playing a neuroprotective role in C elegans model. In addition to information for treatment strategies for neurodegenerative diseases and other diseases caused by age-related protein aggregation.

Kawaguchi Y et al. (1994) Nat Genet "CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1."

Kawaguchi Y, Inoue M, Nishimura M, Kawakami H, Okamoto T, Katayama S, Nakamura S, Aizawa M, Akiguchi I, Taniwaki M

[Nat Genet, 1994]

We have identified a novel gene containing CAG repeats and mapped it to chromosome 14q32.1, the genetic locus for Machado-Joseph disease (MJD). In normal individuals the gene contains between 13 and 36 CAG repeats, whereas most of the clinically diagnosed patients and all of the affected members of a family with the clinical and pathological diagnosis of MJD show expansion of the repeat-number (from 68-79). Southern blot analyses and genomic cloning demonstrates the existence of related genes. These results raise the possibility that similar abnormalities in related genes may give rise to diseases similar to MJD.

Rodrigues AJ et al. (2007) FASEB J "Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3."

Ailion M, Rodrigues AJ, Maciel P, Geschwind DH, Coppola G, Santos C, Costa MD, Sequeiros J

[FASEB J, 2007]

Machado-Joseph disease (MJD) is the most common dominant spinocerebellar ataxia. MJD is caused by a CAG trinucleotide expansion in the ATXN3 gene, which encodes a protein named ataxin-3. Ataxin-3 has been proposed to act as a deubiquitinating enzyme in the ubiquitin-proteasome pathway and to be involved in transcriptional repression; nevertheless, its precise biological function(s) remains unknown. To gain further insight into the function of ataxin-3, we have identified the Caenorhabditis elegans orthologue of the ATXN3 gene and characterized its pattern of expression, developmental regulation, and subcellular localization. We demonstrate that, analogous to its human orthologue, C. elegans ataxin-3 has deubiquitinating activity in vitro against polyubiquitin chains with four or more ubiquitins, the minimum ubiquitin length for proteasomal targeting. To further evaluate C. elegans ataxin-3, we characterized the first known knockout animal models both phenotypically and biochemically, and found that the two C. elegans strains were viable and displayed no gross phenotype. To identify a molecular phenotype, we performed a large-scale microarray analysis of gene expression in both knockout strains. The data revealed a significant deregulation of core sets of genes involved in the ubiquitin-proteasome pathway, structure/motility, and signal transduction. This gene identification provides important clues that can help elucidate the specific biological role of ataxin-3 and unveil some of the physiological effects caused by its absence or diminished function.--Rodrigues, A-J., Coppola, G., Santos, C., do Carmo Costa, M., Ailion, M., Sequeiros, J., Geschwind, D. H., Maciel, P. Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3.

Sudhaus W (1974) Zool. Jb. Syst. Bd. "Zur Systematik, Verbreitung, Okologie und Biologie neuer und wenig bekannter Rhabditiden (Nematoda) 2. Teil."

Sudhaus W

[Zool. Jb. Syst. Bd., 1974]

Five new species of the genus Rhabditis are described (Rh. riemanni n. sp., Rh. remanei n. sp., Rh. reciproca n. sp., Rh. blumi n. sp., and Rh. valida n. sp.) belonging to five subgenera (Crustorhabditis, Caenorhabditis, Rhabditis, Cephaloboides, and Pellioditis). The descriptions of four additional species are revised (Rh. ocypodis Chitwood, Rh. scanica Allgen, Rh. plicata Volk, and Rh. bengalensis Timm). The new subgenus Crustorhabditis n. subgen. derives from the paraphyletic subgenus Mesorhabditis. The species of the former group show a transition from living in littoral seaweed deposits to an obligate association with amphibious crabs (Crustacea). Information about the distribution, ecology, biology and ethology of all these species is presented (with two distribution maps, one for Rh. marina for comparison). Supplementary notes are given from Protorhabditis oxyuroides Sudhaus and Rhabditis tripartita von Linstow.

Pohl F et al. (2024) MicroPubl Biol "Pharmacological inhibition of acetylcholinesterase improves the locomotion defective phenotype of a SCA3 C. elegans model."

Maciel P, Pohl F, Teixeira-Castro A, Lindsay-McGee V, Kong Thoo Lin P

[MicroPubl Biol, 2024]

Inhibition of acetylcholinesterase (AChE) is a common used treatment option for Alzheimer's disease. However, there has been limited research on the potential use of AChE inhibitors for the treatment of Machado-Joseph disease (MJD)/Spinocerebellar Ataxia 3 (SCA3), in spite of the positive results using AChE inhibitors in patients with other inherited ataxias. MJD/SCA3, the most common form of dominant Spinocerebellar Ataxia worldwide, is caused by an expansion of the polyglutamine tract within the ataxin-3 protein, and is characterized by motor impairments. Our study shows that administration of the AChE inhibitor neostigmine is beneficial in treating the locomotion defective phenotype of a SCA3/MJD model of <i>C. elegans</i> and highlights the potential contribution of AChE enzymes to mutant ataxin-3-mediated toxicity.

Teixeira-Castro A et al. (2011) Hum Mol Genet "Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways."

Oliveira JF, Vilaca JL, Brignull HR, Ailion M, Teixeira-Castro A, Dias N, Neves-Carvalho A, Maciel P, Morimoto RI, Jalles A, Rodrigues P

[Hum Mol Genet, 2011]

The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado-Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated pathogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the downregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.