The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte
01 Mar 2013-Nature Reviews Molecular Cell Biology (Nature Publishing Group)-Vol. 14, Iss: 3, pp 141-152
TL;DR: Recent advances in molecular genetics and quantitative live imaging reveal new insights into the molecular basis of the communication between the oocyte and ovarian somatic cells as well as the dynamic cytoskeleton-based events that drive each step along the pathway to maturity.
Abstract: Mammalian oocytes go through a long and complex developmental process while acquiring the competencies that are required for fertilization and embryogenesis. Recent advances in molecular genetics and quantitative live imaging reveal new insights into the molecular basis of the communication between the oocyte and ovarian somatic cells as well as the dynamic cytoskeleton-based events that drive each step along the pathway to maturity. Whereas self-organization of microtubules and motor proteins direct meiotic spindle assembly for achieving genome reduction, actin filaments are instrumental for spindle positioning and the establishment of oocyte polarity needed for extrusion of polar bodies. Meiotic chromatin provides key instructive signals while being 'chauffeured' by both cytoskeletal systems.
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TL;DR: The feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro is described and this knowledge is integrated into the current understanding of cellular actin organizations and its physiological roles.
Abstract: Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles.
1,128 citations
Cites background from "The road to maturation: somatic cel..."
...304), at the site of clathrin mediated endocytosis (335), and is necessary for meotic spindle positioning (177, 348) and for the motility of some bacteria and viruses in host cell cytoplasm (47, 91)....
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TL;DR: Recent technologies are now exploring transcriptional, translational, and post-translational events within the human follicle with the goal of identifying biomarkers that reliably predict oocyte quality in the clinical setting.
402 citations
TL;DR: The importance of oocyte maturation for the achievement of female meiosis has long been recognized, but until recently much less was known of the significance of this process in relation to other fundamental developmental events.
Abstract: Background In a growth phase occurring during most of folliculogenesis, the oocyte produces and accumulates molecules and organelles that are fundamental for the development of the preimplantation embryo. At ovulation, growth is followed by a phase of maturation that, although confined within a short temporal window, encompasses modifications of the oocyte chromosome complement and rearrangements of cytoplasmic components that are crucial for the achievement of developmental competence. Cumulus cells (CCs) are central to the process of maturation, providing the oocyte with metabolic support and regulatory cues. Methods PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews concerning oocyte maturation in mammals. Searches were performed adopting 'oocyte' and 'maturation' as main terms, in association with other keywords expressing concepts relevant to the subject. The most relevant publications, i.e. those concerning major phenomena occurring during oocyte maturation in established experimental models and the human species, were assessed and discussed critically to offer a comprehensive description of the process of oocyte maturation. Results By applying the above described search criteria, 6165 publications were identified, of which 543 were review articles. The number of publications increased steadily from 1974 (n = 7) to 2013 (n = 293). In 2014, from January to the time of submission of this manuscript, 140 original manuscripts and reviews were published. The studies selected for this review extend previous knowledge and shed new and astounding knowledge on oocyte maturation. It has long been known that resumption of meiosis and progression to the metaphase II stage is intrinsic to oocyte maturation, but novel findings have revealed that specific chromatin configurations are indicative of a propensity of the oocyte to resume the meiotic process and acquire developmental competence. Recently, genetic integrity has also been characterized as a factor with important implications for oocyte maturation and quality. Changes occurring in the cytoplasmic compartment are equally fundamental. Microtubules, actin filaments and chromatin not only interact to finalize chromosome segregation, but also crucially co-operate to establish cell asymmetry. This allows polar body extrusion to be accomplished with minimal loss of cytoplasm. The cytoskeleton also orchestrates the rearrangement of organelles in preparation for fertilization. For example, during maturation the distribution of the endoplasmic reticulum undergoes major modifications guided by microtubules and microfilaments to make the oocyte more competent in the generation of intracellular Ca(2+) oscillations that are pivotal for triggering egg activation. Cumulus cells are inherent to the process of oocyte maturation, emitting regulatory signals via direct cell-to-cell contacts and paracrine factors. In addition to nurturing the oocyte with key metabolites, CCs regulate meiotic resumption and modulate the function of the oocyte cytoskeleton. Conclusions Although the importance of oocyte maturation for the achievement of female meiosis has long been recognized, until recently much less was known of the significance of this process in relation to other fundamental developmental events. Studies on chromatin dynamics and integrity have extended our understanding of female meiosis. Concomitantly, cytoskeletal and organelle changes and the ancillary role of CCs have been better appreciated. This is expected to inspire novel concepts and advances in assisted reproduction technologies, such as the development of novel in vitro maturation systems and the identification of biomarkers of oocyte quality.
317 citations
Cites background from "The road to maturation: somatic cel..."
...Development of cell polarity and the ability to undergo highly asymmetric divisions are characteristics that largely rely on self-organizing processes (Li and Albertini, 2013)....
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TL;DR: It is demonstrated that YTH domain-containing 2 (YTHDC2) is an m6A reader that is essential for male and female fertility in mice and reveals a role for YTH DC2 in modulating the levels of m 6A-modified germline transcripts to maintain a gene expression program that is conducive for progression through meiosis.
304 citations
Additional excerpts
...Just before ovulation, the oocyte completes meiosis I, and after fertilization completes meiosis II to become a mature ovum (Li and Albertini, 2013)....
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TL;DR: It is demonstrated that YTHDF2 is autonomously required within the germline to produce MII oocytes that are competent to sustain early zygotic development and is an intrinsic determinant of mammalian oocyte competence and early zig-zag development.
271 citations
Cites background from "The road to maturation: somatic cel..."
...Oocyte maturation is hormonally triggered and occurs just prior to ovulation when GV oocytes complete meiosis I and advance to metaphase II (MII) (Li and Albertini, 2013)....
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...The somatic cells support and transmit key instructive signals to the growing oocyte (Li and Albertini, 2013)....
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TL;DR: Lifeact, a 17-amino-acid peptide, is described, which stained filamentous actin (F-actin) structures in eukaryotic cells and tissues and in its chemically modified peptide form allowed visualization of actin dynamics in nontransfectable cells.
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TL;DR: Oocyte growth and zona pellucida formation proceed normally, but other aspects of oocyte differentiation are compromised, and GDF-9 is the first oocyte-derived growth factor required for somatic cell function in vivo.
Abstract: Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function, but it is unclear whether oocyte-secreted factors play a reciprocal role in modulating somatic cell functions in vivo. During the functional analysis of members of the transforming growth factor-beta superfamily in mouse development, we have uncovered a new family member, growth differentiation factor-9 (GDF-9), which is required for ovarian folliculogenesis. GDF-9 messenger RNA is synthesized only in the oocyte from the primary one-layer follicle stage until after ovulation. Here we analyse ovaries from GDF-9-deficient female mice and demonstrate that primordial and primary one-layer follicles can be formed, but there is a block in follicular development beyond the primary one-layer follicle stage which leads to complete infertility. Oocyte growth and zona pellucida formation proceed normally, but other aspects of oocyte differentiation are compromised. Thus, GDF-9 is the first oocyte-derived growth factor required for somatic cell function in vivo.
1,541 citations
TL;DR: This review summarizes what is known about the biochemical and biophysical mechanisms that initiate the assembly of actin filaments in cells and focuses on Arp2/3 complex and formins.
Abstract: This review summarizes what is known about the biochemical and biophysical mechanisms that initiate the assembly of actin filaments in cells. Assembly and disassembly of these filaments contribute to many types of cellular movements. Numerous proteins regulate actin assembly, but Arp2/3 complex and formins are the focus of this review because more is known about them than other proteins that stimulate the formation of new filaments. Arp2/3 complex is active at the leading edge of motile cells, where it produces branches on the sides of existing filaments. Growth of these filaments produces force to protrude the membrane. Crystal structures, reconstructions from electron micrographs, and biophysical experiments have started to map out the steps through which proteins called nucleation-promoting factors stimulate the formation of branches. Formins nucleate and support the elongation of unbranched actin filaments for cytokinesis and various types of actin filament bundles. Formins associate processively with the fast-growing ends of filaments and protect them from capping.
997 citations