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Bioessays,
2008]
Predicting the phenotype of an organism from its genotype is a central question in genetics. Most importantly, we would like to find out if the perturbation of a single gene may be the cause of a disease. However, our current ability to predict the phenotypic effects of perturbations of individual genes is limited. Network models of genes are one tool for tackling this problem. In a recent study, (Lee et al.) it has been shown that network models covering the majority of genes of an organism can be used for accurately predicting phenotypic effects of gene perturbations in multicellular organisms. BioEssays 30:707-710, 2008. (c) 2008 Wiley Periodicals, Inc.
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Front Cell Dev Biol,
2020]
Cell invasion is defined by the capability of cells to migrate across compartment boundaries established by basement membranes (BMs). The development of complex organs involves regulated cell growth and regrouping of different cell types, which are enabled by controlled cell proliferation and cell invasion. Moreover, when a malignant tumor takes control over the body, cancer cells evolve to become invasive, allowing them to spread to distant sites and form metastases. At the core of the switch between proliferation and invasion are changes in cellular morphology driven by remodeling of the cytoskeleton. Proliferative cells utilize their actomyosin network to assemble a contractile ring during cytokinesis, while invasive cells form actin-rich protrusions, called invadopodia that allow them to breach the BMs. Studies of developmental cell invasion as well as of malignant tumors revealed that cell invasion and proliferation are two mutually exclusive states. In particular, anchor cell (AC) invasion during <i>Caenorhabditis elegans</i> larval development is an excellent model to study the transition from cell proliferation to cell invasion under physiological conditions. This mini-review discusses recent insights from the <i>C. elegans</i> AC invasion model into how G1 cell-cycle arrest is coordinated with the activation of the signaling networks required for BM breaching. Many regulators of the proliferation-invasion network are conserved between <i>C. elegans</i> and mammals. Therefore, the worm may provide important clues to better understand cell invasion and metastasis formation in humans.
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1980]
A number of review articles on the nematode cuticle have been published in the last decade. The most recent of these are those of Bird and Lee and Atkinson. These authors, while emphasizing the complexity and variability of nematode cuticles, support the use of a simplified nomenclature of cuticle structure which divides the cuticle into three regions or zones-namely, cortical, median, and basal. It is obvious that many exceptions to this fundamental pattern occur, and I shall mention some of these below. However, I think that they are adaptations to survival in changing environments, particularly where parasitism is involved. In particular, I propose to consider the structure and functions of the surface or epicuticle of the cortical zone, for it is here that reactions similar to those occurring at cell surfaces and in cell membranes are thought to occur in a wide range of "helminth" organisms. At the moment, particularly for the Nematoda, these ideas require more experimental evidence to establish them as facts. However, the use of sensitive techniques currently employed by membrane physicists and chemists to isolate, label, analyze, measure, and observe interactions taking place in cell membranes have in many instances yet to be used on the nematode cuticle. There is no doubt that the free-living bacterial-feeding nematodes such as those belonging to the genus Caenorhabditis, and in particular C. elegans, are the experimental models of choice for this purpose.
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Biology of the Cell,
1999]
In the Caenorhabditis elegans hermaphrodite, the establishment of the egg-laying system requires the connection of two epithelial tubes: the uterus of the gonad and the vulva in the underlying ectoderm. A specialized uterine cell, the anchor cell (AC), plays a central role in specifying the fates of the uterine and vulval precursor cells via the EGF-Ras-MAP kinase and the Notch/Delta signaling pathways. This central and common inducing source ensures that the two sets of cells are in register and it specifies the cell types that build the T-shaped connection between uterus and vulva. On either side, progeny of the induced cells form lumen structures and undergo stereotyped cell-to-cell fusion, thereby building epithelial tubes. Finally, the anchor cell fuses with a uterine syncytium and thus leaves only a thin cellular process between the lumen of the uterus and the vulva. In the adult, the fertilized eggs exit the lumen of the uterus through the vulva. This relatively simple developmental process serves as a model to study the biology of cells during organogenesis, such as intercellular signaling, cell polarity, invasion of basal laminae and epithelia, cell recognition and cell fusion. The anchor cell is a particularly interesting cell as it coordinates the development of its neighboring cells by using different signaling pathways at different times.
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Crit Rev Biochem Mol Biol,
2012]
The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the "innovative" NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription. The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y - also termed CBF and CP1 - is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on-chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here.