RanGTP and the actin cytoskeleton keep paternal and maternal chromosomes apart during fertilization

Abstract

Zygotes require two accurate sets of parental chromosomes, one each from the mother and the father, to undergo normal embryogenesis. However, upon egg–sperm fusion in vertebrates, the zygote has three sets of chromosomes, one from the sperm and two from the egg. The zygote therefore eliminates one set of maternal chromosomes (but not the paternal chromosomes) into the polar body through meiosis, but how the paternal chromosomes are protected from maternal meiosis has been unclear. Here we report that RanGTP and F-actin dynamics prevent egg–sperm fusion in proximity to maternal chromosomes. RanGTP prevents the localization of Juno and CD9, egg membrane proteins that mediate sperm fusion, at the cell surface in proximity to maternal chromosomes. Following egg–sperm fusion, F-actin keeps paternal chromosomes away from maternal chromosomes. Disruption of these mechanisms causes the elimination of paternal chromosomes during maternal meiosis. This study reveals a novel critical mechanism that prevents aneuploidy in zygotes.

Mysteries and unsolved problems of mammalian fertilization and related topics

“…It largely disappears from the egg surface after fertilization. Although immune cytochemical micrographs of JUNO presented by Bianchi et al [199] and Suzuki et al [200] show that JUNO is on the entire surface of oocyte, those by Mori et al [ 201 ] show no JUNO in the microvilli-free area. It is known that microvilli-free area of the oocyte plasma membrane and the polar body are not capable of fusing with spermatozoa [ 25 ].…”

Fusexins, HAP2/GCS1 and Evolution of Gamete Fusion

“…It is possible that it is involved in membrane merging or in the later incorporation of the sperm. In addition, the actin cytoskeleton might control the position of the sperm during fusion, distancing it from the maternal chromosomes avoiding the elimination of paternal chromosomes during the formation of the second polar body ( Mori et al, 2021 ). Cortical actin dynamics are also required for the correct trafficking of the cortical granules ( Connors et al, 1998 ; Vogt et al, 2019 ), specialized vesicles of the oocyte that contribute to the block of polyspermy after fertilization.…”

Preventing aneuploidy: The groom must wait until the bride is ready

“…Altogether, Mori and colleagues ( 1 ) illustrate here the importance of delaying the fusion of mouse maternal and paternal genomes to ensure proper zygotic development. While the two pronuclei meet in center of the zygote via F-actin and microtubule-dependent mechanisms ( 10 ), it is only in interphase of the two-cell embryo that both parental genomes will potentially mix ( 11 ), attesting to the idea that this occurs quite late in the process.…”

“…In most mammals, fertilization engages the second round of sister chromatid division of the egg, the unwanted chromosomes being extruded into a small degenerating polar body. In this issue, Mori et al ( 1 ) identify mechanisms that prevent the inadvertent encounter of male and female chromosomes until the mouse egg finishes its second meiotic division. These processes are essential to avoid inadvertent elimination of the male genome together with the haploid maternal set.…”

“…Mori et al ( 1 ) first show that two key proteins in sperm fusion to the egg, Juno ( 4 ) and CD9 ( 5 , 6 , 7 ), display a punctate distribution on the egg membrane with a density correlating with that of the microvilli; greater away from maternal chromosomes and lower above the maternal set. Intriguingly, Juno and CD9 are also abundant in the transition zone, rich in lamellipodia-like structures, between the microvilli-poor and -dense regions.…”