Marek Jindra

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. Here, 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 (beta-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.

The molecular action of juvenile hormone (JH), a regulator of vital importance to insects, was until recently regarded as a mystery. The past few years have seen an explosion of studies of JH signaling, sparked by a finding that a JH-resistance gene, Methoprene-tolerant (Met), plays a critical role in insect metamorphosis. Here, we summarize the recently acquired knowledge on the capacity of Met to bind JH, which has been mapped to a particular ligand-binding domain, thus establishing this bHLH-PAS protein as a novel type of an intracellular hormone receptor. Next, we consider the significance of JH-dependent interactions of Met with other transcription factors and signaling pathways. We examine the regulation and biological roles of genes acting downstream of JH and Met in insect metamorphosis. Finally, we discuss the current gaps in our understanding of JH action and outline directions for future research.