Seminars in Developmental Biology最新文献

The sea urchin egg receptor for sperm represents the first example of a gamete recognition protein residing in the egg plasma membrane, the site of the final species-specific interaction with the sperm. The identification and characterization of this unique transmembrane glycoprotein have led to new questions about the molecular basis of gamete recognition and binding as well as egg activation. This review attempts to define and discuss some of these new questions and to point out and begin to resolve several inconsistencies between the molecular and the biological aspects of fertilization.

Aspergillus nidulans is a multicellular fungus being used to study developmental regulation and cell cycle regulation. Genetic and molecular mechanisms underlying both processes have been characterized. Two types of observations suggest that there is significant interaction between cell cycle and developmental regulatory mechanisms. First, A. nidulans development involves the formation of specialized cell types that contain different, but specific, numbers of nuclei that are differentially regulated for cell cycle progression. Second, mutations directly affecting nuclear division can have major affects on cell differentiation during development. In this essay we describe these interactions and point out potential mechanisms for the cross talk between morphogenesis and the cell cycle that are tractable for future experimental investigation.

Our understanding of how meiotic maturation is regulated in Xenopus laevis continues to flourish. Premature initiation of maturation is prevented by the cAMP-dependent protein kinase, which inhibits the synthesis of Mos and potently blocks activation of cdc25. The autoamplification of maturation promoting factor (MPF) activity can be explained by the ability of MPF to directly activate cdc25. Later, in Meiosis II, the contribution of Mos to cytostatic factor (CSF) appears to be mediated through its activation of the mitogen-activated protein kinase, and cdk2 has been added to the active components of CSF. A model is presented illustrating the pathways of meiotic reinitiation, and indicating gaps in our knowledge.

The biochemical pathways underlying the prophase/metaphase transition have been studied extensively in isolated starfish oocytes. These cells are released from their meiotic prophase arrest by 1-methyladenine. This hormone interacts with plasma membrane receptors coupled to heterotrimeric G-proteins. Early events following 1-methyladenine/receptor interaction include a decrease of cAMP concentration and possibly involve tyrosine kinases, phospholipases A2 and C, proteases and phosphatase 2A. Later events include the activation of an M phase-Promoting Factor (MPF) through dephosphorylation/phosphorylation of its p34^cdc2 and cyclin B subunits, MPF translocation to the nucleus and activation of the MAP-kinase p44^mpk. Starfish oocytes provide an exceptional model to investigate a hormone-regulated cell cycle phase as well as a unique source for the purification of cell cycle control elements.

For developmental biology, the most relevant aspect of the cell cycle is presumably the fact that it is not really a perfect cycle. By going from one to two cells, the cycle does not end exactly where it started, but it contributes building blocks for the construction of multicellular organisms. Entry into, progression through, and exit from the cell cycle are controlled during development in order to generate sufficient cells in the correct spatial and temporal pattern. G1- and G2-cyclin-dependent kinases, which govern the progression through the cell cycle, are expected therefore to be regulated by developmental inputs. Analyses in Drosophila have revealed a variety of mechanisms that control the activity of these kinase complexes in different cell cycle types at successive developmental stages.

The isolation of plant genes homologous to cdk and cyclin components from yeast and animals proves the existence of a basic cell cycle machinery in all eukaryotes. cdk and cyclin expression has been shown to be involved in the spatial and temporal control of cell division in a variety of developmental processes. In plants, cell division and development are closely interlinked processes that are regulated by phytohormones. cdks and cyclins were found to be under control of phytohormones underscoring their integral role in mediating different developmental pathways. Furthermore, studies on cdk and cyclin expression not only correlate with actual cell cycle activity but also with cell division competence providing a working model to understand regeneration capacity at the molecular level.

The yeast cell cycle is regulated by a number of different cyclin-Cdc28 complexes, some of which orchestrate G1 events, and some of which orchestrate G2/M events. G1 cyclins lead to expression of G2 cyclins; the G2 cyclins then repress the G1 cyclins. G2 cyclin expression eventually leads to mitosis, which causes loss of the G2 cyclins, allowing derepression and reappearance of the G1 cyclins. These interactions between different classes of cyclins push the yeast cell cycle forward. Nutrients act through the G1 cyclins to stimulate division, while mating pheromones act through G1 cyclins to inhibit division.

Entry into mitosis is a highly regulated process essential for transmission of genetic information to the next generation. Biochemically, in fission yeast and higher eukaryotes, the decision to enter mitosis is mediated by checkpoints that regulate the tyrosine 15 phosphorylation state of Cdc2. The Wee1/mik1 tyrosine kinases and the Cdc25 phosphatase are the enzymes responsible for the phosphorylation/dephosphorylation of tyrosine 15, respectively, and both are also controlled by phosphorylation. In the case of Cdc25, Cdc2-dependent phosphorylation is activating and forms a positive feedback loop, whereas phosphorylation of Wee1 by other kinases is inhibitory. Evidence suggests that periodic changes in both protein phosphatase 1 and 2A also contribute to changes in Wee1 and Cdc25 activity during the cell cycle. Exit from mitosis is also a highly regulated process with potential checkpoint controls. The metaphase arrest of vertebrate eggs in Meiosis II by the mos protooncogene product is an apparent consequence of the ability of mos to phosphorylate and activate MAP kinase kinase and may involve cooperation with Cdk2/cyclin E.

The mouse oocyte provides a system in which it is possible to follow the behaviour and activity of the major components of the cell cycle control machinery and their principle cellular targets the chromosomes and the microtubules. In this article, we summarize our present knowledge of the interplay between the cell cycle control machinery and the microtubule network during the meiotic maturation and after activation of the mouse oocytes.