Masako Asahina et al. (2006) European Worm Meeting "Interplay Between the Nuclear Receptor NHR-25 and ?-Catenin Signaling during Cell Fate Decision in the Gonad of C. elegans"

Marek JINDRA, Masako ASAHINA, Marie SILHANKOVA, Vladimir Korinek, Tomas Valenta

[European Worm Meeting, 2006]

Interplay Between the Nuclear Receptor NHR-25 and ?-Catenin Signaling during Cell Fate Decision in the Gonad of C. elegans. Masako Asahina, Tomas Valenta3, Marie Silhankova2, Vladimir Korinek3 and Marek Jindra. Molecular mechanisms that specify cell fates during asymmetric cell divisions are critical for differentiation. In the somatic gonad precursors (SGPs) of Caenorhabditis elegans, a ?-catenin pathway plays a crucial role in the proximal-distal fate decision. The Wnt nuclear effector TCF/POP-1 and ?-catenins WRM-1 and SYS-1 are the key molecules for this decision. Impaired function of all of these genes leads to a Sys (Symmetrical sisters) phenotype, when all SGPs adopt the same, proximal fate. Thus, no distal tip cells (DTCs) that would lead germline differentiation and elongation of the gonadal arms are formed in hermaphrodites. Here, we show that a loss of the nuclear receptor NHR-25 (a homolog of SF-1 and Ftz-F1) causes an extra DTC phenotype, where up to four DTCs form at the expense of proximally fated the anchor cell. This all-distal Sys phenotype is thus opposite to known loss-of-function phenotypes of genes in the ?-catenin pathway. Our data show that a balance between the ?-catenin/POP-1 activity and the action of NHR-25 is required for the proper establishment of both the distal and proximal cell fates. pop-1(q645) mutants that never form DTCs and consequently lack gonadal arms develop DTCs, extend the gonadal arms, and become fertile when nhr-25 is silenced in them. By using cell transfection techniques, co-immunoprecipitation and yeast two-hybrid assays, we show that this interaction is coordinated by mutual modulation of NHR-25 and POP-1 activities through direct contacts of NHR-25 with the distinct ?-catenins WRM-1 and SYS-1. The crosstalk between nuclear receptor and ?-catenin signaling thus establishes the proper axis of the entire organ.. Supported by projects Z60220518, Czech Acad. Sci., and 6007665801 from the Czech Ministry of Education.

Masako Asahina et al. (2006) Development & Evolution Meeting "Crosstalk between Nuclear Receptor NHR-25 and β-Catenin Signaling Decides Cell Fates in the C. elegans Somatic Gonad"

Tomas Valenta, Masako ASAHINA, Vladimir Korinek, Marek JINDRA, Marie SILHANKOVA

[Development & Evolution Meeting, 2006]

Recent findings indicate that nuclear receptor and Wnt/β-catenin signaling pathways intersect during important processes such as cell differentiation, proliferation or malignant growth. In the somatic gonad precursors (SGPs) of Caenorhabditis elegans, a β-catenin pathway plays a crucial role in the proximal-distal cell fate decision. The Wnt nuclear effector TCF/POP-1 and β-catenins WRM-1 and SYS-1 are the key molecules for this decision. Impaired function of all of the respective genes leads to a Sys (Symmetrical sisters) phenotype, when all SGPs adopt the same, proximal fate. Thus, no distal tip cells (DTCs) that would lead germline differentiation and elongation of the gonadal arms are formed in hermaphrodites. Here, we show that loss of the nuclear receptor NHR-25 (a homolog of SF-1, LRH-1 and Ftz-F1) causes an extra DTC phenotype, where up to four DTCs form at the expense of the proximally fated anchor cell. This “all-distal” Sys phenotype is thus opposite to known loss-of-function phenotypes of genes in the β-catenin pathway. Our data show that a balance between the β-catenin/POP-1 activity and the action of NHR-25 is required for the proper establishment of both the distal and proximal cell fates. pop-1(q645) mutants that never form DTCs and consequently lack gonadal arms develop DTCs, extend the gonadal arms, and become fertile when nhr-25 is silenced in them. By using cell transfection techniques, co-immunoprecipitation, yeast two-hybrid and GST pulldown assays, we show that this interaction is coordinated by mutual modulation of NHR-25 and POP-1 activities through direct contacts of NHR-25 with the distinct β-catenins WRM-1 and SYS-1. The crosstalk between nuclear receptor and β-catenin signaling thus establishes the proper axis of the entire organ. The C. elegans gonad can serve as a unique example of how nuclear receptor and β-catenin signaling pathways intersect to govern fate decision of specific cells. Supported by projects Z60220518, Czech Acad. Sci., and 6007665801 from the Czech Ministry of Education.

Keiko Mase et al. (2004) East Asia Worm Meeting "A secretory protein OSM-7 is involved in not only chemotaxis but also resistance to high osmolarity"

Takeshi Ishihara, Makoto Koga, Keiko Mase, Yasumi Ohshima

[East Asia Worm Meeting, 2004]

In Caenorhabditis elegans , chemotaxis to water soluble chemicals is very important behavior to find their food, but the mechanisims have not been fully elucidated. A lot of mutants which showed chemotaxis defects had been isolated and studied, and most of them had abnormal sensory neurons. By studying them, essential molecules for the development and morphology of the nervous system were identified. However we do not know well the molocules for cell signaling specifically regulating this behavior. We started to analyze behavioral mutants which have normal sensory cilia, because, by this analysis, we think it possible to find such new molecules. We are studying on osm-7(n1515) mutant, which was isolated by Tomas and Horvitz (1988). osm-7 shows abnoramlities in osmotic avoidance and chemotaxis to sodium ion, althogh, according to dye filling experiment, it has normal sensory cilia in amphid neurons. We found a new phenotype in osm-7 ; osm-7 is resistant to high osmolarity. osm-7 amimals are able to survive on plate containing 800mM NaAc, whereas wild type animals can not survive more than a few minutes. Most of other osm mutants examined did not show resistance to high osmolarity. These results indicate that osmotic avoidance and osmotic resistance are not closely linked phenotypes. Using SNP-snips mapping and rescue experiments with YAC clones and PCR fragments, we identified the osm-7 gene to be T05D4.4. Also, we found a mutation site in this gene of osm-7(n1515) by sequencing. OSM-7 consists of 651 amino acid residues with a signal peptide, suggesting that OSM-7 is a secretory protein. We think that OSM-7 is a novel protein and we could not find any homologue in Drosophila nor human genome. The expression of a fusion of T05D4.4 with green fluorescent protein (GFP) is clearly seen especially in hypodermis. Though the construct has rescueing activity for chemotaxis defect and osmotic resitance, we could not see the expression in the nerve cells. That expression pattern was unexpected. We will elucidate how OSM-7 regulates chemotaxis to sodium ion and resistance to high osmolarity by analyzing where and when OSM-7 is needed in animals.

Hernandez-Gonzalez A et al. (2016) Parasit Vectors "Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes."

Aparicio P, Garate T, Nguema J, Moya L, Nguema R, Hernandez-Gonzalez A, Perteguer MJ, Benito A, Herrador Z

[Parasit Vectors, 2016]

BACKGROUND: Onchocerciasis or "river blindness" is a chronic parasitic disease caused by the filarial worm Onchocerca volvulus, transmitted through infected blackflies (Simulium spp.). Bioko Island (Equatorial Guinea) used to show a high endemicity for onchocerciasis. During the last years, the disease control programmes using different larvicides and ivermectin administration have considerably reduced the prevalence and intensity of infection. Based on this new epidemiological scenario, in the present work we aimed to assess the impact of the strategies applied against onchocerciasis in Bioko Island by an evaluation of IgG4 antibodies specific for recombinant Ov-16 in ELISA. METHODS: A cross-sectional study was conducted in Bioko Island from mid-January to mid-February, 2014. Twenty communities were randomly selected from rural and urban settings. A total of 140 households were chosen. In every selected household, all individuals aged 5years and above were recruited; 544 study participants agreed to be part of this work. No previous data on onchocerciasis seroprevalence in the selected communities were available. Blood samples were collected and used in an "ELISA in-house" prepared with recombinant Ov-16, expressed and further purified. IgG4 antibodies specific for recombinant Ov-16 were evaluated by ELISA in all of the participants. RESULTS: Based on the Ov-16 ELISA, the onchocerciasis seroprevalence was 7.9%, mainly concentrated in rural settings; samples from community Catedral Ela Nguema (# 16) were missed during the field work. Among the rural setups, communities Inasa Maule (# 7), Ruiche (# 20) and Barrios Adyacentes Riaba (# 14), had the highest seropositivity percentages (29.2, 26.9 and 23.8%, respectively). With respect to the urban settings, we did not find any positive case in communities Manzana Casa Bola (# 3), Colas Sesgas (# 6), Getesa (# 8), Moka Bioko (# 9), Impecsa (# 10), Baney Zona Baja (# 12) and Santo Tomas de Aquino (# 1). No onchocerciasis seropositive samples were found in 10-year-old individuals or younger. The IgG4 positive titles increased in older participants. CONCLUSIONS: A significant decline in onchocerciasis prevalence was observed in Bioko Island after years of disease-vector control and CDTI strategy. The seroprevalence increased with age, mainly in rural settings that could be due to previous exposure of population to the filarial parasite, eliminated by the control programmes introduced against onchocerciasis. A new Ov-16 serological evaluation with a larger sample size of children below 10years of age is required to demonstrate the interruption of transmission of O. volvulus in the human population of Bioko Island (Equatorial Guinea) according to the WHO criteria.