Cell scientist to watch – Binyam Mogessie

ABSTRACT Binyam Mogessie was born and raised in Ethiopia. He moved to Germany in 2004, where he studied biochemistry and cell biology at Jacobs University Bremen. He then moved to the UK for his PhD with Anne Straube, first at the Marie Curie Research Institute in Surrey and later at the Centre for Mechanochemical Cell Biology in Warwick, where he investigated the cellular mechanisms that organise the microtubule cytoskeleton during skeletal muscle differentiation. After receiving his PhD in cell biology from the University of London, he joined the laboratory of Melina Schuh in 2012 as a postdoc at the MRC-LMB in Cambridge (and later at the Max Planck Institute in Göttingen, Germany), where he discovered a function of the actin cytoskeleton in accurate chromosome segregation and the prevention of aneuploidy in mammalian eggs. Binyam established his independent research laboratory at the University of Bristol, School of Biochemistry in 2018, where he is a Wellcome Trust and Royal Society Sir Henry Dale fellow and HFSP Young Investigator. He also received a Seed Award from the Wellcome Trust and funding from the Rosetrees Trust and Royal Society. His lab is investigating actin- and microtubule-based cytoskeletal ensembles that promote healthy egg development and embryogenesis in mammals.

ZP4 Is Present in Murine Zona Pellucida and Is Not Responsible for the Specific Gamete Interaction

Mammalian eggs are surrounded by an extracellular matrix called the zona pellucida (ZP). This envelope participates in processes such as acrosome reaction induction, sperm binding, protection of the oviductal embryo, and may be involved in speciation. In eutherian mammals, this coat is formed of three or four glycoproteins (ZP1–ZP4). While Mus musculus has been used as a model to study the ZP for more than 35 years, surprisingly, it is the only eutherian species in which the ZP is formed of three glycoproteins Zp1, Zp2, and Zp3, Zp4 being a pseudogene. Zp4 was lost in the Mus lineage after it diverged from Rattus, although it is not known when precisely this loss occurred. In this work, the status of Zp4 in several murine rodents was tested by phylogenetic, molecular, and proteomic analyses. Additionally, assays of cross in vitro fertilization between three and four ZP rodents were performed to test the effect of the presence of Zp4 in murine ZP and its possible involvement in reproductive isolation. Our results showed that Zp4 pseudogenization is restricted to the subgenus Mus, which diverged around 6 MYA. Heterologous in vitro fertilization assays demonstrate that a ZP formed of four glycoproteins is not a barrier for the spermatozoa of species with a ZP formed of three glycoproteins. This study identifies the existence of several mouse species with four ZPs that can be considered suitable for use as an experimental animal model to understand the structural and functional roles of the four ZP proteins in other species, including human.

The prophase oocyte nucleus is a homeostatic G-actin buffer

Formation of healthy mammalian eggs from oocytes requires specialised F-actin structures. F-actin disruption produces aneuploid eggs, which are a leading cause of human embryo deaths, genetic disorders, and infertility. We found that oocytes regulate F-actin organisation and function by promptly transferring excess monomeric G-actin from the cytoplasm to the nucleus. Inside healthy oocyte nuclei, transferred monomers form dynamic F-actin structures, a conserved feature that significantly declines with maternal age. Monomer transfer must be controlled tightly. Blocked nuclear import of G-actin triggers assembly of a dense cytoplasmic F-actin network, while excess G-actin in the nucleus dramatically stabilises nuclear F-actin. Imbalances in either direction predispose oocytes to aneuploidy. The large oocyte nucleus is thus a homeostatic G-actin buffer that is used to maintain cytoplasmic F-actin form and function.One Sentence SummaryMammalian oocyte nuclei buffer cytosolic G-actin

Zinc protection of fertilized eggs is an ancient feature of sexual reproduction in animals

One of the earliest and most prevalent barriers to successful reproduction is polyspermy, or fertilization of an egg by multiple sperm. To prevent these supernumerary fertilizations, eggs have evolved multiple mechanisms. It has recently been proposed that zinc released by mammalian eggs at fertilization may block additional sperm from entering. Here, we demonstrate that eggs from amphibia and teleost fish also release zinc. Using Xenopus laevis as a model, we document that zinc reversibly blocks fertilization. Finally, we demonstrate that extracellular zinc similarly disrupts early embryonic development in eggs from diverse phyla, including: Cnidaria, Echinodermata, and Chordata. Our study reveals that a fundamental strategy protecting human eggs from fertilization by multiple sperm may have evolved more than 650 million years ago.

Perfect date—the review of current research into molecular bases of mammalian fertilization

Fertilization is a multistep process during which two terminally differentiated haploid cells, an egg and a sperm, combine to produce a totipotent diploid zygote. In the early 1950s, it became possible to fertilize mammalian eggs in vitro and study the sequence of cellular and molecular events leading to embryo development. Despite all the achievements of assisted reproduction in the last four decades, remarkably little is known about the molecular aspects of human conception. Current fertility research in animal models is casting more light on the complexity of the process all our lives start with. This review article provides an update on the investigation of mammalian fertilization and highlights the practical implications of scientific discoveries in the context of human reproduction and reproductive medicine.

Simultaneous Deletion of Transient Receptor Potential Vanilloid 3 and Cacna1h Undermines Ca2+ Homeostasis in Oocytes and Fertility in Mice

In mammals, calcium (Ca2+) influx fills the endoplasmic reticulum, from where Ca2+ is released following fertilization to induce egg activation. However, an incomplete index of the plasma membrane channels and their specific contributions that underlie this influx in oocytes and eggs led us to simultaneously knock out the transient receptor potential vanilloid, member 3 (TRPV3) channel and the T-type channel, CaV3.2. Double knockout (dKO) females displayed subfertility and their oocytes and eggs showed significantly diminished Ca2+ store content and oscillations after fertilization compared to controls. We also found that the cell cycle stage during maturation determines the functional expression of channels whereby they show a distinct permeability to certain ions. In total, we demonstrate that TRPV3 and CaV3.2 are required for initiating physiological oscillations and that Ca2+ influx dictates the periodicity of oscillations during fertilization. dKO gametes will be indispensable to identify the complete native channel currents present in mammalian eggs.