mutants also exhibited a reduced brood size, increased embryonic lethality and a High Incidence of Males (Him) at the nonpermissive heat, all phenotypes indicative of increased meiotic chromosome nondisjunction (Table 1). Table 1. Worms were maintained at 15C and then shifted Daminozide to 25C at the L4 larval stage. at the terminal third of every pair of homologous chromosomes, we proposed that chromosomes remodel around the single off-centered CO event at the pachytene-diplotene transition. This results in bivalents with a cruciform configuration comprised of two perpendicular chromosomal axes (namely the long and short arm domains) intersecting at the chiasma, where the long arms face the poles and the short arms occupy an equatorial position around the metaphase plate (Physique 1A) (Nabeshima et al., 2005; Riddle et al., 1997; Maddox et al., 2004). This remodeling includes changes in chromosome compaction as well as changes in both the localization and the types of proteins associated with the long and short arm domains (Physique 1A) (Nabeshima et al., 2005; Chan et al., 2004; de Carvalho et al., 2008; Martinez-Perez and Villeneuve, 2005). Subsequent studies in yeast, flies and mice (Newnham et al., 2010; Qiao et al., 2012; Bisig et al., 2012; Takeo et al., 2011; Gladstone et al., 2009) also observed an asymmetric disassembly of the SC, with a residual localized retention Daminozide of the SC at centromeres. However, the mechanism linking CO recombination sites to asymmetric SC disassembly remained unknown. Open in a separate window Physique 1. ECT-2 regulates AIR-2 localization and SC dynamics in meiotic prophase I.(A) Schematic representation of SC dynamics and chromosome remodeling during prophase I of meiosis. A single pair of homologous chromosomes (bivalent) is usually shown for simplicity. Upon entrance into pachytene, the SC is present along the full length of the pairs of homologous chromosomes. CO formation is usually completed within the context of fully synapsed chromosomes, and in worms, a single CO is usually formed per homolog pair usually at an off-centered position. Chromosome remodeling has been proposed to take place around the off-centered CO (or CO precursor) resulting in a cruciform configuration comprised of two intersecting perpendicular chromosomal axes of different lengths (long and short arms of the bivalent, corresponding to the longest and shortest distances from the off-centered CO/CO precursor site to opposite ends of the chromosomes). This remodeling involves disassembly of central region components of the SC (SYP-1/2/3/4) along the long arms of the GRIA3 bivalents starting during late pachytene and diplotene resulting in the restricted localization of these proteins to the short arms. During diplotene and diakinesis, chromosomes undergo condensation as evidenced by a coiling of the arms and increased bivalent compaction. In late diakinesis, the SC Daminozide proteins located on the short arms are replaced by AIR-2, which promotes the separation of the homologs at the end of meiosis I. CO C crossover, S C short arm and L C long arm. (B) Immunolocalization of HTP-3 and AIR-2 on -1 oocytes at diakinesis in wild type, and gonads. AIR-2 is usually localized to the short arm of the bivalents in wild type and mutants, but fails to localize onto chromosomes in mutants. Diagrams on the right illustrate the cruciform structure of the bivalents at this stage consisting of long (L) and short (S) arms and the localization of AIR-2 (red) and HTP-3 (green) in wild type and mutant. White box indicates the bivalent shown at a higher magnification on the right. Bivalents with both long and short arms clearly displayed were chosen for higher magnification. (C) Immunolocalization of HTP-3 and SYP-1 on leptotene/zygotene nuclei from gonads of the indicated genotypes. SYP-1 aggregates (polycomplexes) are detected in mutants. (D) SYP-1 and HTP-3 localize throughout the full length of the synapsed homologous chromosomes.