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.