Parental Control Begins at the Beginning

Abstract

In this commentary, Diana Chu considers the findings of Ataeian et al. (2016) in this issue of GENETICS in the context of parental contributions to development. This work reveals how molecular players contributed by oocyte and sperm coordinate early transitions in the embryo.N ew parents anticipate their job begins at birth. Little do they know they have been exerting control within the baby's first cell since fertilization. At that moment, sperm entry unleashes a torrent of molecular changes crucial for development. A key transition is forming the diploid DNA complement from paternal and maternal DNA. Sperm bring their haploid share to the oocyte; however, preparing the maternal haploid portion is carefully staged. Oocytes, which can be stored for years in some organisms, arrest prior to meiotic divisions until receiving a signal to begin meiotic maturation (Figure 1). Oocytes start meiotic divisions but arrest again until fertilization signals egg activation. At that point, meiotic divisions complete, and the cell transitions to mitosis. This transition from oocyte to embryo is vital-the cell must sense that the paternal DNA is in the house before completing the meiotic divisions. The molecules that coordinate these early events are largely mysterious in any organism, due in part to the difficulty of observing fertilization within living organisms. In this issue, Ataeian et al. (2016) exploit tools offered by the transparent model organism Caenorhabditis elegans to identify and characterize maternal and paternal molecular components that together convey that fertilization has occurred, and embryonic development is ready to proceed.The maternal part of the story began with a classical temperaturesensitive genetic screen in C. elegans performed 20 years ago to identify genes important for embryonic development (Mitenko et al. 1997). Ataeian et al. (2016) focus on a dominant maternal effect lethal mutant called sb41. Examining an sb41 strain expressing fluorescently tagged histone and tubulin proteins revealed that oocytes do not transition to embryos properlythey fail to complete the second meiotic division, do not form a second polar body, and enter mitosis with the wrong complement of maternal DNA. Subsequently, the cell fails to complete mitosis and dies. Based on this phenotype, the authors dub the affected gene memi-1 (meiosis-to-mitosis transition defect).Whole genome sequencing of the mutant allowed researchers to molecularly characterize memi-1. Database searches revealed two C. elegans paralogs, named memi-2 and memi-3, that share 87% identity with memi-1 but have no conserved domains. Genetic and RNAi analyses showed that single mutants or knockdowns of individual memi genes exhibit no phenotypes, whereas reducing expression of at least two memi paralogs together causes embryonic lethality, supporting the view that MEMI proteins work redundantly. This function is regulated in a cell cycledependent manner, as MEMI levels are high in oocytes but low in mitosis. The authors show that ubiquitin-mediated pr...