Asymmetric cell division and differentiation of cells are the keys to form a multicellular organism from a single cell. Caenorhabditis elegans provides us great tools to disect the molecular mechanisms of these events genetically and to visually track cells at single-cell resolution during development. We are particularly interested in the role of the ancient nuclear receptor family NR5A, also called SF-1/LRH-1 in mammals, Ftz-F1 in invertebrates, amphibians, reptiles and fish, and NHR-25 in C. elegans, in cell differentiation and interaction with other important signaling cascades such as Wnt/ß-catenin, Runx, Ras pathways.
Hada K., Asahina M., Hasegawa H., Kanaho Y., Slack F.J., Niwa R. (2010) The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition. Developmental Biology 344: 1100-1109.
Seetharaman A., Cumbo P., Bojanala N., Gupta B.P. (2010) Conserved mechanism of Wnt signaling function in the specification of vulval precursor fates in C. elegans and C. briggsae. Developmental Biology 346: 128–139.
HAJDUŠKOVÁ M., JINDRA M., HERMAN M.A., ASAHINA M. (2009) The nuclear receptor NHR-25 cooperates with Wnt/ß-catenin asymmetry pathway to control T cell differentiation in C. elegans. Journal of Cell Science 122: 3051-3060.
We have found that NHR-25 is involved in the specification of gonadal precursor cells in C. elegans. Somatic gonadal cells called Z1/Z4 divide asymmetrically to produce proximally fated and distally fated cells in postembryonic development. When the NHR-25 level is reduced by RNAi, this cell fate determination is disturbed and the proximal cell was transformed into a distal cell. The important regulatory pathway, Wnt signaling, is known to be crucial in this proximal-distal specification and we show genetically that NHR-25 interacts with Wnt/ß-catenin pathway. Furthermore we analyze the mechanism of its action by showing direct interactions of NHR-25 and ß-catenins proteins. Interplay between nuclear receptors and Wnt signaling pathway is a newly emerging yet important concept.
Cell fate specification of the gonad in C. elegans. The lineage (left) shows the Z1/Z4 cell division in wild type. nhr-25(RNAi) disturbs the proper distal-proximal specification and extra DTCs (distal tip cells) are formed instead of proximally fated AC (anchor cell).
Cell fate specification of the gonad in C. elegans. The lineage (left) shows the Z1/Z4 cell division in wild type. nhr-25(RNAi) disturbs the proper distal-proximal specification and extra DTCs (distal tip cells) are formed instead of proximally fated AC (anchor cell).
Asymmetric cell divisions produce new cell types during animal development. Studies in Caenorhabditis elegans have identified major signal-transduction pathways that determine the polarity of cell divisions. How these relatively few conserved pathways interact and what modulates them to ensure the diversity of multiple tissue types is an open question. The Wnt/beta-catenin asymmetry pathway governs polarity of the epidermal T seam cell in the C. elegans tail. We show that the asymmetry of T-seam-cell division and morphogenesis of the male sensory rays require NHR-25, an evolutionarily conserved nuclear receptor. NHR-25 ensures the neural fate of the T-seam-cell descendants in cooperation with the Wnt/beta-catenin asymmetry pathway. Loss of NHR-25 enhances the impact of mutated nuclear effectors of this pathway, POP-1 (TCF) and SYS-1 (ß-catenin), on T-seam-cell polarity, whereas it suppresses the effect of the same mutations on asymmetric division of the somatic gonad precursor cells. Therefore, NHR-25 can either synergize with or antagonize the Wnt/beta-catenin asymmetry pathway depending on the tissue context. Our findings define NHR-25 as a versatile modulator of Wnt/beta-catenin-dependent cell-fate decisions.
Morphogenesis of vulva involves various genetical regulatory pathways such as EGF, Ras, MAPK, Notch, Runx and Wnt and it is a great model to study interaction and modulation of these pathways. When the funciton of NHR-25 is attenuated, the formation of vulva is defective and we try to understand underling mechanism of this defect. We follow the morphology and the fate of the vulval cells utilizing various transgenes fused with a fluorscent protein such as GFP expressed in wild type and mutant live worms.
A large collection of helminths is available for comparative studies...
