miRNAs give worms the time of their lives: small RNAs and temporal control in Caenorhabditis elegans.

Alteration in the timing of particular developmental events can lead to major morphological changes that have profound effects on the life history of an organism. Insights into developmental timing mechanisms have been revealed in the model organism Caenorhabditis elegans, in which a regulatory network of heterochronic genes times events during larval development, ensuring that stage-specific programs occur in the appropriate sequence and on schedule. Developmental timing studies in C. elegans led to the landmark discovery of miRNAs and continue to enhance our understanding of the regulation and activity of these small regulatory molecules. Current views of the heterochronic gene pathway are summarized here, with a focus on the ways in which miRNAs contribute to temporal control and how miRNAs themselves are regulated. Finally, the conservation of heterochronic genes and their functions in timing, as well as their related roles in stem cells and cancer, are highlighted.

Mutations in the chromosomal passenger complex and the condensin complex differentially affect synaptonemal complex disassembly and metaphase I configuration in Drosophila female meiosis.

Production of haploid gametes relies on the specially regulated meiotic cell cycle. Analyses of the role of essential mitotic regulators in meiosis have been hampered by a shortage of appropriate alleles in metazoans. We characterized female-sterile alleles of the condensin complex component dcap-g and used them to define roles for condensin in Drosophila female meiosis. In mitosis, the condensin complex is required for sister-chromatid resolution and contributes to chromosome condensation. In meiosis, we demonstrate a role for dcap-g in disassembly of the synaptonemal complex and for proper retention of the chromosomes in a metaphase I-arrested state. The chromosomal passenger complex also is known to have mitotic roles in chromosome condensation and is required in some systems for localization of the condensin complex. We used the QA26 allele of passenger component incenp to investigate the role of the passenger complex in oocyte meiosis. Strikingly, in incenp(QA26) mutants maintenance of the synaptonemal complex is disrupted. In contrast to the dcap-g mutants, the incenp mutation leads to a failure of paired homologous chromosomes to biorient, such that bivalents frequently orient toward only one pole in prometaphase and metaphase I. We show that incenp interacts genetically with ord, suggesting an important functional relationship between them in meiotic chromosome dynamics. The dcap-g and incenp mutations cause maternal effect lethality, with embryos from mutant mothers arrested in the initial mitotic divisions.

INCENP and Aurora B promote meiotic sister chromatid cohesion through localization of the Shugoshin MEI-S332 in Drosophila.

The chromosomal passenger complex protein INCENP is required in mitosis for chromosome condensation, spindle attachment and function, and cytokinesis. Here, we show that INCENP has an essential function in the specialized behavior of centromeres in meiosis. Mutations affecting Drosophila incenp profoundly affect chromosome segregation in both meiosis I and II, due, at least in part, to premature sister chromatid separation in meiosis I. INCENP binds to the cohesion protector protein MEI-S332, which is also an excellent in vitro substrate for Aurora B kinase. A MEI-S332 mutant that is only poorly phosphorylated by Aurora B is defective in localization to centromeres. These results implicate the chromosomal passenger complex in directly regulating MEI-S332 localization and, therefore, the control of sister chromatid cohesion in meiosis.