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      Mouse SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis

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          Abstract

          During meiosis, the arrangement of homologous chromosomes is tightly regulated by the synaptonemal complex (SC). Each SC consists of two axial/lateral elements (AEs/LEs), and numerous transverse filaments. SC protein 2 (SYCP2) and SYCP3 are integral components of AEs/LEs in mammals. We find that SYCP2 forms heterodimers with SYCP3 both in vitro and in vivo. An evolutionarily conserved coiled coil domain in SYCP2 is required for binding to SYCP3. We generated a mutant Sycp2 allele in mice that lacks the coiled coil domain. The fertility of homozygous Sycp2 mutant mice is sexually dimorphic; males are sterile because of a block in meiosis, whereas females are subfertile with sharply reduced litter size. Sycp2 mutant spermatocytes exhibit failure in the formation of AEs and chromosomal synapsis. Strikingly, the mutant SYCP2 protein localizes to axial chromosomal cores in both spermatocytes and fetal oocytes, but SYCP3 does not, demonstrating that SYCP2 is a primary determinant of AEs/LEs and, thus, is required for the incorporation of SYCP3 into SCs.

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          Most cited references55

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          A drying-down technique for the spreading of mammalian meiocytes from the male and female germline.

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            The genetics and molecular biology of the synaptonemal complex.

            The synaptonemal complex (SC) is a protein lattice that resembles railroad tracks and connects paired homologous chromosomes in most meiotic systems. The two side rails of the SC, known as lateral elements (LEs), are connected by proteins known as transverse filaments. The LEs are derived from the axial elements of the chromosomes and play important roles in chromosome condensation, pairing, transverse filament assembly, and prohibiting double-strand breaks (DSBs) from entering into recombination pathways that involve sister chromatids. The proteins that make up the transverse filaments of the SC also play a much earlier role in committing a subset of DSBs into a recombination pathway, which results in the production of reciprocal meiotic crossovers. Sites of crossover commitment can be observed as locations where the SC initiates and as immunostaining foci for a set of proteins required for the processing of DSBs to mature crossovers. In most (but not all) organisms it is the establishment of sites marking such crossover-committed DSBs that facilitates completion of synapsis (full-length extension of the SC). The function of the mature full-length SC may involve both the completion of meiotic recombination at the DNA level and the exchange of the axial elements of the two chromatids involved in the crossover. However, the demonstration that the sites of crossover formation are designated prior to SC formation, and the finding that these sites display interference, argues against a role of the mature SC in mediating the process of interference. Finally, in at least some organisms, modifications of the SC alone are sufficient to ensure meiotic chromosome segregation in the complete absence of meiotic recombination.
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              An abundance of X-linked genes expressed in spermatogonia.

              Spermatogonia are the self-renewing, mitotic germ cells of the testis from which sperm arise by means of the differentiation pathway known as spermatogenesis. By contrast with hematopoietic and other mammalian stem-cell populations, which have been subjects of intense molecular genetic investigation, spermatogonia have remained largely unexplored at the molecular level. Here we describe a systematic search for genes expressed in mouse spermatogonia, but not in somatic tissues. We identified 25 genes (19 of which are novel) that are expressed in only male germ cells. Of the 25 genes, 3 are Y-linked and 10 are X-linked. If these genes had been distributed randomly in the genome, one would have expected zero to two of the genes to be X-linked. Our findings indicate that the X chromosome has a predominant role in pre-meiotic stages of mammalian spermatogenesis. We hypothesize that the X chromosome acquired this prominent role in male germ-cell development as it evolved from an ordinary, unspecialized autosome.
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                Author and article information

                Journal
                J Cell Biol
                JCB
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                22 May 2006
                : 173
                : 4
                : 497-507
                Affiliations
                [1 ]Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
                [2 ]Female Germ Cell Biology Group, Department of Clinical Studies, [3 ]Department of Animal Biology, and [4 ]Center for Animal Transgenesis and Germ Cell Research, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348
                Author notes

                Correspondence to P. Jeremy Wang: pwang@ 123456vet.upenn.edu

                Article
                200603063
                10.1083/jcb.200603063
                2063860
                16717126
                b0d251fd-8afa-418a-b766-9d75a465d58e
                Copyright © 2006, The Rockefeller University Press
                History
                : 14 March 2006
                : 18 April 2006
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

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