Komatsu H et al. (2008) PLoS Biol "OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development."

Chao MY, Boxem M, Dionne HM, Somers GA, Wani K, Tucey T, Corkins ME, Larkins-Ford J, White JQ, Hart AC, Komatsu H

[PLoS Biol, 2008]

Notch signaling is critical for cell fate decisions during development. Caenorhabditis elegans and vertebrate Notch ligands are more diverse than classical Drosophila Notch ligands, suggesting possible functional complexities. Here, we describe a developmental role in Notch signaling for OSM-11, which has been previously implicated in defecation and osmotic resistance in C. elegans. We find that complete loss of OSM-11 causes defects in vulval precursor cell (VPC) fate specification during vulval development consistent with decreased Notch signaling. OSM-11 is a secreted, diffusible protein that, like previously described C. elegans Delta, Serrate, and LAG-2 (DSL) ligands, can interact with the lineage defective-12 (LIN-12) Notch receptor extracellular domain. Additionally, OSM-11 and similar C. elegans proteins share a common motif with Notch ligands from other species in a sequence defined here as the Delta and OSM-11 (DOS) motif. osm-11 loss-of-function defects in vulval development are exacerbated by loss of other DOS-motif genes or by loss of the Notch ligand DSL-1, suggesting that DOS-motif and DSL proteins act together to activate Notch signaling in vivo. The mammalian DOS-motif protein Deltalike1 (DLK1) can substitute for OSM-11 in C. elegans development, suggesting that DOS-motif function is conserved across species. We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates.

Winkenbach LP et al. (2019) RNA Biol "Todos Santos small RNA symposium."

Claycomb JM, Doser R, Pasquinelli AE, Winkenbach LP, Reed KJ, Phillips CM

[RNA Biol, 2019]

Worm biologists from the United States, Canada, and the United Kingdom gathered at the Colorado State University Todos Santos Center in Baja California Sur, Mexico, April 3-5, 2019 for the Todos Santos Small RNA Symposium. Meeting participants, many of whom were still recovering from the bomb cyclone that struck a large swath of North America just days earlier, were greeted by the warmth and sunshine that is nearly ubiquitous in the sleepy seaside town of Todos Santos. With only 24 speakers, the meeting had the sort of laid-back vibe you might expect amongst the palm trees and ocean breeze of the Pacific coast of Mexico. The meeting started with tracing the laboratory lineages of participants. Not surprisingly, the most common parental lineages represented at the meeting were Dr. Craig Mello, Dr. Gary Ruvkun, and Dr. Victor Ambros, whom, together with Dr. Andy Fire and Dr. David Baulcombe, pioneered the small RNA field. In sad irony, on the closing day of the meeting, participants were met with the news of Dr. Sydney Brenner's passing. By establishing the worm, <i>Caenorhabditis elegans</i>, as a model system Dr. Brenner paved the way for much of the research discussed here.

Liu Y et al. (2002) FEBS Lett "The gift of Gab."

Liu Y, Rohrschneider LR

[FEBS Lett, 2002]

Gab proteins, including mammalian Gab1, Gab2, Gab3, Drosophila DOS and Caenorhabditis elegans Soc1, comprise a growing family of scaffolding/docking molecules involved in multiple signaling pathways mediated by receptor tyrosine kinases (RTKs) and non-RTK receptors. This paper reviews the structure/function relationships of Gab proteins and their biological roles during normal growth, differentiation and development programs.

Edgley ML (1990) Worm Breeder's Gazette "New Versions of the CGC Bibliography, Strain List and Map Data"

Edgley ML

[Worm Breeder's Gazette, 1990]

New paper versions of the CGC Strain List, the second part of the bibliography (1986 through the present) and the complete map data will be available toward the middle of July, 1990. The strain list and bibliography will be sent automatically to every lab with a CGC designation and they are free upon request to anyone else (one per lab, please). The map data printouts are very large (>800 pages), and are special-request items. If your lab does a lot of genetics and relies on these printouts, you're welcome to have one. (I have a small list of people who have asked for one already; don't worry, I haven't forgotten you.) The CGC Bibliography is published in two parts. Part I covers 1866 through 1985 and is not regularly updated. Part II covers everything from January, 1986, and will be updated every two years until it is equal in size to Part I, when a new single list will be generated. Copies of Part I are still available if you don't have one. As usual, all of these lists are available as simple delimited text files for either Macintosh or DOS computers. To get a copy of any or all computer files, send me the appropriate number and type of blank diskettes with a request letter. The files will fit on two 1.2 Mb 5. 25' floppies (MS-DOS), two 700 Kb 3.5' floppies (MS-DOS or Mac) or one 1.44 Mb 3.5' floppy (MS-DOS or Mac).

Sorkac, Altar et al. (2011) International Worm Meeting "Notch signaling regulates synaptic transmission at the neuromuscular junction."

Singh, Komudi, Hart, Anne, Sorkac, Altar, DiIorio, Michael

[International Worm Meeting, 2011]

The role of Notch signaling during development has been characterized in many organisms, including the nematode C. elegans. In the canonical pathway, Notch receptors are cleaved by the g-secretase/presenilin complex upon ligand binding, releasing the intracellular domain that enters the nucleus to act as a transcription factor. In C. elegans, Notch receptors LIN-12 and GLP-1 are activated by DSL ligands working with DOS-motif proteins that act as co-activators. Here, we show that Notch signaling impacts synaptic transmission. Loss of two DOS co-ligands, OSM-7 and OSM-11, resulted in hypersensitivity to inhibitors of cholinesterase (Hic) on aldicarb. glp-1(gf) or glp-1(lf) had no impact on aldicarb response; whereas lin-12 null animals were Hic and lin-12(gf) mutants were Ric (Resistance to inhibitors of cholinesterase). These findings suggest a model in which OSM-7 and OSM-11 act on LIN-12 Notch receptors to regulate synaptic transmission at the neuromuscular junction.

Zhang Z et al. (2024) Nat Commun "DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells."

Yang H, Fang L, Xiang J, Zhao G, Zheng JC, Qin Z, Zhang Z

[Nat Commun, 2024]

Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.

Sorkac, Altar et al. (2013) International Worm Meeting "Notch signaling regulates synaptic transmission at the C. elegans neuromuscular junction."

Hart, Anne, Sorkac, Altar, Graham, Hannah, Singh, Komudi, DiIorio, Michael

[International Worm Meeting, 2013]

Notch is a signaling pathway that has been conserved across the animal kingdom. The role of Notch signaling during nervous system development has been extensively studied whereas its effects outside cell fate specification are less well described. Notch signaling is active in adult mice, Drosophila and C. elegans, regulating synaptic activity and other neurobiological processes. Notch receptors LIN-12 and GLP-1 are activated by DSL proteins with DOS-motif proteins acting as co-ligands. In C. elegans, Notch signaling affects avoidance of aversive chemicals and quiescence. Intriguingly, Notch DOS co-ligands OSM-7 and OSM-11 are regulated by environmental osmolarity; animals lacking either one of these co-ligands are preadapted to osmotic stress. Here, we show that Notch signaling impacts synaptic transmission at the neuromuscular junction of C. elegans, possibly in this neuroethological context. Complete loss of the Notch receptor LIN-12 results in hypersensitivity to aldicarb (Hic), an inhibitor of acetylcholinesterase. Loss the DSL ligand DSL-3 or either DOS co-ligand, OSM-7 or OSM-11, also results in hypersensitivity; these ligands likely activate LIN-12 in this paradigm. Notch signaling in adults is sufficient as overexpression of OSM-11 exclusively in adult animals causes resistance to aldicarb (Ric). Moreover, knock-down by RNAi of osm-11 in early larval stages does not cause adult aldicarb hypersensitivity. Also, osm-11 knock-down after the L2 larval stage results in hypersensitivity. Loss of the transcription factor LAG-1 resulted in hypersensitivity to aldicarb suggesting that LIN-12 signals via the canonical pathway. Next, the site of action of LIN-12 will be elucidated and candidate downstream targets will be examined in order to further our understanding of how Notch signaling regulates synaptic transmission.

Alves, Carla et al. (2021) International Worm Meeting "The effects of venlafaxine on behavior and central nervous system of Caenorhabditis elegans"

Vanin, Ana Paula, dos Santos, Amanda, Sutorillo, Nathalia Tafarel, Barcellos, Leonardo Jose Gill, Santini, Wallace, Alves, Carla, Tamagno, Wagner Antonio, Kaizer Perin, Rosilene Rodrigues

[International Worm Meeting, 2021]

The growing consumption of psychoactive drugs, including antidepressants and antipsychotics, along with the low levels of total metabolization of these drugs, are increasing their residues in the environment. After being used, the drugs are metabolized and excreted, sometimes still in their active form, and may or may not suffer degradation when in contact with the environment. Thus, these psychoactive drugs can reach the aquatic environment and affect non-target organisms, such as zebrafish (Danio rerio) and Caenorhabditis elegans, in their natural environments. Our main hypothesis is that venlafaxine (VEN), a drug that works with the selective inhibition of the reuptake of noradrenaline and serotonin, can exert effects on the endocrine and behavioral system of zebrafish and toxicological effects on the behavior and nervous system of C. elegans. The integrity of the natural behavioral repertoire is vital for the maintenance of the species, reinforcing the importance of studies that show the potential of drugs in altering these models. Here we evaluate acute exposure to VEN, in three concentrations followed by a behavioral assessment. The behavior of C. elegans was analyzed by the body bands, pharyngeal beat, and defecation cycle; while the biochemical analyzes of the enzyme Acetylcholinesterase to assess the toxicological effects of VEN on the nervous system. We have shown that the nematode C. elegans resists changes in behavior and the nervous system. Thus, this model response was not a clear indicator of water contamination and possible zebrafish effects, probably because of the cuticle and natural behavior of the nematode. Results with zebrafish exposure to VEN have shown changes in the novel tank test, mainly the robust anxiolytic-like pattern, suggesting that VEN may be more dangerous to species conservation, since fish presenting an anxiolytic-like behavior becomes more susceptible to predation. We are working on biomarkers to study differences in the responses to these models when exposed at VEN.

Tamagno, Wagner Antoino et al. (2021) International Worm Meeting "Protective and reparative effect of dragon fruit upon central nervous system toxicity induced by copper"

Tamagno, Wagner Antoino, Sutorillo, Nathalia Tafarel, Alves, Carla, dos Santos, Amanda, Kaizer, Rosilene Rodrigues, Barcellos, Leonardo Jose Gill, Santini, Wallace, Vanin, Ana Paula

[International Worm Meeting, 2021]

Copper is an essential metal and is important in general metabolism. However, in high concentrations, it becomes toxic to the organism. The metal-induced toxicity is linked to many neurodegenerative diseases like Parkinson's, Alzheimer's, multiple sclerosis, occurring in senile aging. To prevent neurodegenerative diseases, some studies are being developed to find ways of healthy aging. Natural compounds and diets based on fruits are increasing. Dragon fruit (Hylocereus undatus) is a tropical and Latin American fruit that is gaining more popularity due to its antioxidant properties. This fruit still has low popularity, since its planting and large-scale commercialization are recent. Here we evaluate the protective and reparative effect of different doses of dragon fruit's microencapsulated pulp extract on copper-induced toxicity. The nematode Caenorhabditis elegans was used as a model, to research the effects of pitaya extract on the Cholinergic nervous system, behavior, lipidic peroxidation, and chaperon system. We observed that Cu severally increased directly the cholinesterase, chaperone, and peroxidation rates. When pitaya is applied, even to prevent or remediate, all those enzymes' rates are normalized again. Overall, the results have shown that the pulp fruit extract can be used on dietary supplementation to prevent and repair neural damage. The extract was able to regulates the chaperone system to reduce expression of heat shock protein (16.2) and reestablished the AChE levels avoiding lipidic peroxidation. Changes in the behavior, decreasing cell death biomarkers, and lipidic peroxidation caused by copper toxicity are showing, and, based on these results, we concluded that the pitaya fruit has an important role in gerontological issues.

Schutzman J et al. (2001) Mol Cell Biol "The Caenorhabditis elegans EGL-15 signaling pathway implicates a DOS-like multisubstrate adaptor protein in fibroblast growth factor signal transduction."

Borland CZ, Schutzman J, Stern MJ, Newman JC, Kokel M, Robinson MK

[Mol Cell Biol, 2001]

EGL-15 is a fibroblast growth factor receptor in the nematode Caenorhabditis elegans. Components that mediate EGL-15 signaling have been identified via mutations that confer a Clear (CIr) phenotype, indicative of hyperactivity of this pathway, or a suppressor-of-Clr (Soc) phenotype, indicative of reduced pathway activity. We have isolated a gain-of-function allele of let-60 ras that confers a Cir phenotype and implicated both let-60 ras and components of a mitogen-activated protein kinase cascade in EGL-15 signaling by their Soc phenotype. Epistasis analysis indicates that the gene soc-1 functions in EGL-15 signaling by acting either upstream of or independently of LET-60 RAS. soc-1 encodes a multisubstrate adaptor protein with an amino-terminal pleckstrin homology domain that is structurally similar to the DOS protein in Drosophila and mammalian GAB1. DOS is known to act with the cytoplasmic tyrosine phosphatase Corkscrew (CSW) in signaling pathways in Drosophila. Similarly, the C. elegans CSW ortholog PTP-2 was found to be involved in EGL-15 signaling. Structure-function analysis of SOC-1 and phenotypic analysis of single and double mutants are consistent with a model in which SOC-1 and PTP-2 act together in a pathway downstream of EGL-15 and the Src homology domain 2 (SH2)/SH3-adaptor protein SEM-5/GRB2 contributes to SOC-1-independent activities of EGL-15.