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.

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 C. 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.

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. O RGANISMS that undergo sexual reproduction utilize a specialized cell cycle, meiosis, to generate haploid gametes. Precise partitioning of the genome in meiosis is essential so that diploidy is reestablished upon fertilization, which is critical for embryonic development (Hassold and Hunt 2001). Meiosis employs distinct regulatory mechanisms such that the DNA is replicated exactly once and then divided twice without an additional intervening round of replication.In preparation for meiotic divisons, homologs pair and, in many systems, a proteinaceous structure, the synaptonemal complex (SC), forms an axis between homologs and regulates meiotic recombination (Page and Hawley 2003). Crossover events generate covalent linkages between homologs. These, in combination with sister-chromatid cohesion distal to the chiasmata (the physical structures resulting from crossing over), allow homologs to remain physically attached after SC disassembly and to thereby coordinate their movements.In meiosis I, homologs biorient on the spindle while sister chromatids coorient toward a single pole (reviewed in Petronczki et al. 2003). Release of cohesion distal to the chiasmata at the onset of anaphase I allows homologs to move apart; maintenance of centromere cohesion holds sister chromatids together as they travel toward a single spindle pole. The enduring attachment between sister chromatids is essential for them to biorient on the spindle in meiosis II. Centromere cohesion is severed at the onset of anaphase ...