Nat Rev Genet. evidence for an important role of proper SC disassembly in configuring a functional bivalent structure. INTRODUCTION Meiosis is a specialized cell division that leads to the formation of haploid gametes, which in metazoans are the sperm and egg cells. It involves two cellular divisions after one cycle of replication; in the first (MI), homologous chromosomes segregate away from each other, and in the second (MII), sister chromatids separate (Figure 1A). During meiotic prophase Ithe period preceding the first meiotic divisionchromosomes are organized in the form of bivalents: pairs of homologous chromosomes connected by crossovers and sister chromatid cohesion. Proper bivalent structure is crucial for accurate meiotic division, and defects in its formation lead to improper chromosome segregation, embryonic lethality, and/or birth defects (Hassold and Hunt, 2001 ). Thus an elaborate sequence of events must be orchestrated to form a functional bivalent, which includes two Adamts1 major processes occurring in meiotic prophase I: the establishment of crossovers (early events) and the restructuring of the bivalent to form a compact structure (mid to late prophase I). Open in a separate window FIGURE 1: SC disassembly defects observed in mutants are specific to central region proteins. (A) Schematic representation of chromosome behavior in meiosis, highlighting key events in SC disassembly. Chromosomes are in blue. Central region proteins/SYPs are in red, and axis and axis-associated proteins are in green and yellow. (B) Schematic representation of the predicted AKIR-1 protein. The -helical domain is in blue. The region of the protein deleted in the mutant allele is indicated (underlined amino acids 1C91, 42% of the protein). Half of the predicted promoter is also removed by but is not shown here. The red letter H indicates the position of the histidine mutated to proline in the allele. (CCL) mutants exhibit aggregation of SYP-1, atypical bivalent structure (DCG, inset), and persistence of SYP-1 in diakinesis C1 (HCL). and alleles do not complement each other (E, J). Arrows in CCG point to the regions enlarged in the inset. Insets show separate channels: top, DAPI; bottom, SYP-1. (M) Number of SYP-1 aggregates or patches per oocyte associated with chromosomes (blue) or not associated with chromosomes (red) at diakinesis C1 and diakinesis C3. At diakinesis C3 almost all wild-type diakinesis bivalents associate with SYP-1, found as a patch in the short-arm region. mutants at this stage exhibit similar levels of association of SYP-1 aggregates with chromosomes (Fisher’s exact test, = 0.49, = 0.59). At diakinesis C1 almost all wild-type diakinesis bivalents lack SYP-1, whereas mutants oocyte still contain approximately five SYP-1 aggregates (Fisher’s exact test, 0.001), many of which still associated with chromosomes. The values for number of oocytes scored are indicated on the graph. Error bars are SD, and statistically significant values (MannCWhitney test, 0.001) are indicated with asterisk. (NCS) High-magnification images of DAPI- and HIM-3Cstained nuclei of gonads. High-magnification images of DAPI-stained (blue) and SYP-1C (red, CCL) or HIM-3Cstained (red, NCS) nuclei of gonads from age-matched wild type (C, H, N, Q), (D, I, O, R), (E, J), (F, K, P, S), and (G, L) at diakinesis C3 (CCG, NCP) and diakinesis C1 GSK-5498A (HCL, QCS). Images are full projections of a single nucleus. Bars, 2 m. In most organisms, the formation of at least one crossover event per bivalent necessitates each chromosome finding its partner (pairing) and tightly associating with it (synapsing) via the synaptonemal complex (SC). The SC is a widely conserved protein structure that physically connects homologous chromosomes in meiotic prophase I to mediate synapsis (Zickler and Kleckner, 1999 ). The SC is composed GSK-5498A of two lateral elements (composed of axis-associated proteins) connected by central region proteins that form a zipper-like structure. This results in a tripartite complex that holds homologous chromosomes together until crossovers are formed. Crossovers then trigger SC disassembly along with condensation, which allows the visual manifestation GSK-5498A of the crossover eventthe chiasma (Schvarzstein late meiotic prophase I, each bivalent is reconfigured around the single off-centered crossover as an asymmetric cruciform structure, containing long and short arms (Schvarzstein (MacQueen orthologue of fly and mouse mutants, early meiotic events such as SC assembly and crossover formation occur normally. However, late.
Related Stories
October 24, 2024
May 4, 2023