The Maternal-to-Zygotic Transition in C. elegans

Scott Robertson1; Rueyling Lin    Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas, USA
1 Corresponding author: email address: scott.robertson@utsouthwestern.edu

1 Introduction

In mammalian embryos, primary oocytes initiate meiosis, then arrest at prophase of meiosis I, and remain so until puberty. Cyclical hormone surges lead to a small group of oocytes resuming meiosis and arresting a second time at metaphase of meiosis II. Following ovulation, meiosis completes if the egg is fertilized (Fig. 1A). This cycle continues in mammals over a period of months, years, or even decades (reviewed in Von Stetina & Orr-Weaver, 2011). The Drosophila oocyte differentiates as one member of an interconnected 16-cell cyst, with the other 15 cells forming polyploid nurse cells that support oocyte growth (Von Stetina & Orr-Weaver, 2011). The oocyte arrests at prophase I and then is induced to undergo meiotic maturation by an unknown extrinsic signal, although prostaglandin hormones or ecdysone are likely candidates. On meiotic maturation, the Drosophila oocyte arrests for a second time at metaphase I (Fig. 1A). The signal to resume meiosis in Drosophila is, surprisingly, independent of fertilization, requiring instead the mechanical stress associated with passage through the oviduct (Mahowald, Goralski, & Caulton, 1983). It is thought that this represents a holdover from an ancestral form that reproduced asexually, as some extant Drosophila species, such as Drosophila mercatorum, are capable of parthenogenic development (Eisman & Kaufman, 2007). However, it can lead to the seemingly wasteful situation where eggs can be laid that have not been fertilized.

Free-living, solitary Caenorhabditis elegans are self-fertilizing hermaphrodites and offer several distinct advantages for the study of oocyte development, maturation, fertilization, and the maternal-to-zygotic transition (MZT). The adult body, including the germline, is transparent and the germline develops in a highly spatially ordered, linear manner. A C. elegans hermaphrodite generates sperm in the L3 larval stage, which are stored in the spermatheca, and then switches completely to the generation of oocytes in the L4 larval stage, continuing to do so for the remainder of its reproductive life (Hirsh, Oppenheim, & Klass, 1976; Schedl, 1997). Hermaphrodites contain two tube-like syncytial gonad arms (Fig. 1B). In each gonad, nuclei in the distal region divide mitotically to provide continuing supplies of new germ nuclei. As nuclei move away from the distal region, they initiate and progress through different stages of meiosis, cellularize, and grow in volume in an assembly line-like fashion. The fully grown oocytes undergo maturation, are ovulated through the spermatheca, and are fertilized. Meiosis is completed upon fertilization and embryonic development initiates within the uterus, where the embryos again line up in developmental order before expulsion through the vulva during gastrulation (Fig. 1B).

The MZT includes both initiation within the embryo of transcription of select genes (zygote genome activation, ZGA), as well as inactivation of many maternal mRNAs and proteins that functioned to regulate developmental events following fertilization. The actual timing of the onset of the MZT, as well as its duration, can vary considerably between species. For C. elegans, no zygotic transcription occurs in late oocytes or early embryos prior to the 4-cell stage. In fact, zygotic transcription is not needed for embryos to develop normally—including the stereotypic asymmetric early cleavages, orientation of cleavage planes, and lineage-specific timing of early divisions—until the time when gastrulation should occur, at the 28-cell stage. However, a number of processes are already underway in the developing and maturing oocytes that directly or indirectly affect the MZT. For the purpose of this review, we will describe C. elegans MZT as from late-stage oocytes to approximately 28-cell embryos. An overriding theme of C. elegans MZT regulation is that it is controlled primarily posttranscriptionally and posttranslationally. We aim to show how the combination of asymmetric partitioning of maternal factors, protein modification-mediated changes in function, protein degradation, and highly regulated translational repression ensures a smooth transition.

We will divide the MZT into four key components: (1) oocyte maturation, ovulation, and fertilization; (2) the transition from meiosis to mitosis; (3) the special case of the C. elegans 1-cell embryo; and (4) the transition from a single-cell embryo to a multicell embryo, including the initiation of zygotic transcription. We will review our current understanding of these processes and discuss how they are coordinated one to another and to the cell cycle. We will also highlight four important regulators/events that play key roles in coordinating this transition.

The MZT in C. elegans demonstrates nicely how genetics, cell biology, and biochemistry can be brought to bear upon a highly complex developmental process in a model organism. While genetic screens led to the isolation of mutations defective in individual processes and, thereby, key genes in each process, cell biological and biochemical analyses allowed us to determine how these separate events are precisely timed and coordinated.

2 Components of the MZT

2.1 Oocyte Maturation, Ovulation, and Fertilization

The details of oocyte maturation, ovulation, and fertilization have been reviewed recently elsewhere (Kim, Spike, & Greenstein, 2013; Marcello, Singaravelu, & Singson, 2013; Marcello & Singson, 2010), and we direct readers there for a more complete discussion on these topics.

The solitary worm has...