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Schleiffer, A.

Publications and source records attributed to Schleiffer, A..

2 recordsLinked to original sources

ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice

Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a critical component of complexes of DSB-promoting proteins which assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution owing to reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects are accompanied by a genome-wide delay in assembling DSB-promoting proteins on axes and a loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated complexes of DSB-promoting proteins.

cell biology

The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization

Fertilization is fundamental for sexual reproduction, yet its molecular mechanisms are poorly understood. Here, we identify an oocyte-expressed Ly6/uPAR protein, which we call Bouncer, as a crucial fertilization factor in zebrafish. We show that membrane-bound Bouncer mediates sperm-egg binding and is thus essential for sperm entry into the egg. Remarkably, Bouncer is not only required for sperm-egg interaction, but also sufficient to allow cross-species fertilization between zebrafish and medaka, two fish species that diverged over 150 million years ago. Our study thus identifies Bouncer as a key determinant of species-specific fertilization in fish. Bouncers closest homolog in tetrapods, SPACA4, is restricted to the male gonad in internally fertilizing vertebrates, suggesting that our findings in fish have relevance to human biology.

developmental biology