Metazoan oocyte and early embryo development program: a progression through translation regulatory cascades.

All metazoans that reproduce sexually have the ability to form gametes. The two types of gametes, the egg and the sperm, arise from germ cells, undergo extensive differentiation, and are destined to unite. The outcome of their union, the zygote, maintains and propagates the characteristics of the species. The zygote inherits from the egg not only genetic material but also its cytoplasm, which supports the development of the early embryo through precise expression patterns of maternally inherited messages. The hierarchical organization of these translation regulatory mechanisms is unveiled in the report by Padmanabhan and Richter (2006) in this issue of Genes & Development. Mechanisms for establishing the germline and carrying out oogenesis in evolutionarily distant animals exhibit certain common themes. Gametes develop from primordial germ cells (PGC) that are set aside during early embryogenesis (Matova and Cooley 2001). In most metazoans, PGCs have an extragonadal origin and migrate to reach the somatic gonad, where they proliferate by mitosis to form oocytes in females (Matova and Cooley 2001). Oocytes, in turn, enter meiosis, only to be arrested at the prophase of the first meiotic division (Sagata 1996). This first meiotic arrest may last up to a few years in Xenopus or several decades in humans, and is characterized by synthesis and storage of large quantities of dormant mRNA (LaMarca et al. 1973; Rodman and Bachvarova 1976). When later translated, these maternal mRNAs drive the oocyte’s re-entry into meiosis (Gebauer et al. 1994; Stebbins-Boaz et al. 1996; Mendez et al. 2000) and control the rate of mitosis during the cleavage divisions after fertilization (Groisman et al. 2000; Oh et al. 2000; Uto and Sagata 2000). The resumption of meiosis marks the onset of oocyte maturation and is stimulated by progesterone in Xenopus (Bayaa et al. 2000; Tian et al. 2000) and by gonadotropins in mouse and human (Faiman and Ryan 1967; Rao et al. 1974). In almost all vertebrates, nuclear and cytoplasmic changes associated with oocyte maturation are completed by the metaphase of the second meiotic division, when oocytes become arrested for a second time and await fertilization (Sagata 1996). A complex network of translational activation and repression of stored maternal mRNAs accompanies oocyte maturation (Gebauer et al. 1994; Stebbins-Boaz et al. 1996; Mendez et al. 2000; Oh et al. 2000), while transcription is limited at best. The transcriptional silencing that begins with oocyte maturation persists during the initial mitotic divisions of the embryo, which, unlike any other, lack an appreciable G1 or G2 phase. In Xenopus, after 12 rapid synchronous cleavages, when the developing embryo is composed of ∼4000 cells, the mid-blastula transition occurs and is characterized by lengthening of the cell cycle, inclusion of G1 and G2, and activation of zygotic transcription (Newport and Kirschner 1982a,b). In mouse and human, induction of transcription in the embryo occurs at the two-cell, and fourto eight-cell stages, respectively (Clegg and Piko 1982; Flach et al. 1982; Braude et al. 1988). Despite the earlier occurrence of zygotic transcription, activation of maternally inherited mRNAs in mammals seems to use translation mechanisms similar to those in other vertebrates (Richter 1999; Oh et al. 2000). On a molecular level, it is known that meiotic reactivation is initiated by translation of specific maternal messages such as those encoding rapid inducer of G2/M progression in oocytes/Speedy (RINGO/Spy), cyclin B1, and cyclin-dependent protein kinase 2 (Cdk2) (Ferby et al. 1999; Mendez and Richter 2001; Eichenlaub-Ritter and Peschke 2002; Dekel 2005). Translation of the RINGO/Spy message is essential since the RINGO/Spy protein, a novel cell cycle regulator with unique kinasebinding and activation domains, is required to activate Cdk2 (Ferby et al. 1999; Lenormand et al. 1999; Terret et al. 2001; Cheng et al. 2005). The subsequent action of these gene products is followed by Aurora A/Eg2 protein kinase activation, which, in turn, promotes polyadenylation of specific transcripts including that of mos serine/ threonine kinase (Fig. 1, see orange boxes). Mos is essenThese authors contributed equally to this work. Corresponding author. E-MAIL joan.steitz@yale.edu; FAX (203) 624-8213. Article and publication are at http://www.genesdev. org/cgi/doi/10.1101/ gad.1398906.