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Results for “multicellular coordination”

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PubMed2005

Establishment of oocyte population in the fetal ovary: primordial germ cell proliferation and oocyte programmed cell death.

Strict control of cell proliferation and cell loss is essential for the coordinated functions of different cell populations in complex multicellular organisms. Oogenesis is characterized by a first phase occurring during embryo-fetal life and in common with spermatogenesis, during which mitotic proliferation of the germline stem cells, the primordial germ cells (PGC), prevails over germ cell death. The result is the formation of a relatively high number of germ cells depending on the species, ready to enter sex specific differentiation. In the female, PGC enter into meiosis and become oocytes, thereby ending their stem cell potential. After entering into meiosis in the fetal ovary, oocytes pass through leptotene, zygotene and pachytene stages before arresting in the last stage of meiotic prophase I, the diplotene or dictyate stage at about the time of birth. The most part of oocytes die during the fetal period or shortly after birth. It is widely accepted that in mammals a female is born with a fixed number of oocytes within the ovaries, which over the years progressively decreases without possibility for renewal. Once the oocyte reserve has been exhausted, ovarian senescence, driving what is referred to as the menopause in women, rapidly ensues. The fertile lifespan of a female depends by the size of the oocyte pool at birth and the rapidity of the oocyte pool depletion. Which mechanisms control PGC proliferation? Why do most of the oocytes die during fetal life and what are the mechanisms of such massive degeneration? Is it possible to prolong the lifespan of a female by reducing oocyte lost during the fetal life? This review reports some of the most recent results obtained in an attempt to answer these questions.

Animals↗

PubMed2006

Quorum signal molecules as biosurfactants affecting swarming in Rhizobium etli.

Swarming motility is suggested to be a social phenomenon that enables groups of bacteria to coordinately and rapidly move atop solid surfaces. This multicellular behavior, during which the apparently organized bacterial populations are embedded in an extracellular slime layer, has previously been linked with biofilm formation and virulence. Many population density-controlled activities involve the activation of complex signaling pathways using small diffusible molecules, also known as autoinducers. In Gram-negative bacteria, quorum sensing (QS) is achieved primarily by means of N-acylhomoserine lactones (AHLs). Here, we report on a dual function of AHL molecules in controlling swarming behavior of Rhizobium etli, the bacterial symbiotic partner of the common bean plant. The major swarming regulator of R. etli is the cinIR QS system, which is specifically activated in swarming cells by its cognate AHL and other long-chain AHLs. This signaling role of long-chain AHLs is required for high-level expression of the cin and rai QS systems. Besides this signaling function, the long-chain AHLs also have a direct role in surface movement of swarmer cells as these molecules possess significant surface activity and induce liquid flows, known as Marangoni flows, as a result of gradients in surface tension at biologically relevant concentrations. These results point to an as-yet-undisclosed direct role of long-chain AHL molecules as biosurfactants.

4-Butyrolactone↗

PubMed1995

Pharmacologic control of intracellular signaling pathways: from research to therapy.

Intracellular signaling pathways mediate the main events in a cell's life cycle, such as growth, proliferation, differentiation, performance of specialized functions, and apoptosis. Intracellular signaling is initiated either by extracellular signals or by intracellular gene products, e.g., those resulting from appropriately or inappropriately activated oncogenes. Extracellular signals either are generated by the general environment or are secretory products of other cells (e.g., growth factors, cytokines, hormones). Both act on specific receptors and, with some similarities to endogenous products, activate intracellular signaling and cell functional responses. Extracellular and intracellular signals coordinate the activities of the various cells in multicellular organisms. Dysregulation of signaling pathways by extracellular stimuli such as pathogens, or by gene abnormalities such as oncogene activation or loss of tumor suppressor gene activity, induces disease. The usual therapeutic targets of drugs are the stimuli and, in cancer, the oncogene or its direct product, the mRNA. Molecular components of cell signaling pathways are candidate targets for therapy. This approach may itself be sufficient to modify the positive or negative effects of a molecule in the signaling pathway. Drugs targeting cell signaling molecules can be combined with drugs acting on oncogenes, extracellular stimuli, or receptors. The main molecules involved in intracellular signaling are those of the transduction pathways and the second messengers and transcription factors. These molecules and their interactions are first recalled and are then analyzed to determine how, by the use of "specific" inhibitors, antisense methods, and directed mutagenesis, their functionality has been established. Finally, we will consider whether or not these methods can be adapted to clinical use.

Animals↗

PubMed1988

A chemoattractant receptor controls development in Dictyostelium discoideum.

During the early stages of its developmental program, Dictyostelium discoideum expresses cell surface cyclic adenosine monophosphate (cyclic AMP) receptors. It has been suggested that these receptors coordinate the aggregation of individual cells into a multicellular organism and regulate the expression of a large number of developmentally regulated genes. The complementary DNA (cDNA) for the cyclic AMP receptor has now been cloned from lambda gt-11 libraries by screening with specific antiserum. The 2-kilobase messenger RNA (mRNA) that encodes the receptor is undetectable in growing cells, rises to a maximum at 3 to 4 hours of development, and then declines. In vitro transcribed complementary RNA, when hybridized to cellular mRNA, specifically arrests in vitro translation of the receptor polypeptide. When the cDNA is expressed in Dictyostelium cells, the undifferentiated cells specifically bind cyclic AMP. Cell lines transformed with a vector that expresses complementary mRNA (antisense) do not express the cyclic AMP receptor protein. These cells fail to enter the aggregation stage of development during starvation, whereas control and wild-type cells aggregate and complete the developmental program within 24 hours. The phenotype of the antisense transformants suggests that the cyclic AMP receptor is essential for development. The deduced amino acid sequence of the receptor reveals a high percentage of hydrophobic residues grouped in seven domains, similar to the rhodopsins and other receptors believed to interact with G proteins. It shares amino acid sequence identity and is immunologically cross-reactive with bovine rhodopsin. A model is proposed in which the cyclic AMP receptor crosses the bilayer seven times with a serine-rich cytoplasmic carboxyl terminus, the proposed site of ligand-induced receptor phosphorylation.

Amino Acid Sequence↗

PubMed2001

Cdc5 interacts with the Wee1 kinase in budding yeast.

Development of a multicellular organism requires that mitosis and morphogenesis be coordinated. These processes must also be synchronized during the growth of unicellular organisms. In the yeast Saccharomyces cerevisiae, mitosis is dependent on the prior growth of a daughter cell in the form of a bud. Overexpression of wild-type Polo-like kinase Cdc5 or a catalytically inactive form resulted in the formation of multinucleate cells in budding yeast. Immunofluorescence analysis of these multinulceate cells showed that mitosis and bud formation were no longer linked. Others have shown that Swe1 is required for coupling mitosis to bud formation during a perturbed cell cycle. When the normal pathway of bud formation is perturbed, Swe1 functions to delay mitosis through negative regulation of Clb/Cdk. In cells lacking Swe1, multinucleate cells are formed in response to delays in bud formation. Affinity purification, two-hybrid analysis, and mutant characterization results suggested that Cdc5 and Swe1 interact. From these results, we conclude that multinucleate formation in response to Cdc5 overexpression is linked to titration of Swe1 function. These results also suggest that Cdc5 may be a negative regulator of Swe1.

Cell Cycle Proteins↗

PubMed1999

Modeling chemotactic cell sorting during Dictyostelium discoideum mound formation.

Coordinated cell movement is a major mechanism of the multicellular development of most organisms. The multicellular morphogenesis of the slime mould Dictyostelium discoideum, from single cells into a multicellular fruiting body, results from differential chemotactic cell movement. During aggregation cells differentiate into prestalk and prespore cells that will form the stalk and spores in the fruiting body. These cell types arise in a salt and pepper pattern after what the prestalk cells chemotactically sort out to form a tip. The tip functions as an organizer because it directs the further development. It has been difficult to get a satisfactory formal description of the movement behavior of cells in tissues. Based on our experiments, we consider the aggregate as a drop of a viscous fluid and show that this consideration is very well suited to mathematically describe the motion of cells in the tissue. We show that the transformation of a hemispherical mound into an elongated slug can result from the coordinated chemotactic cell movement in response to scroll waves of the chemoattractant cAMP. The model calculations furthermore show that cell sorting can result from differences in chemotactic cell movement and cAMP relay kinetics between the two cell types. During this process, the faster moving and stronger signaling cells collect on the top of the mound to form a tip. The mound then extends into an elongated slug just as observed in experiments. The model is able to describe cell movement patterns in the complex multicellular morphogenesis of Dictyostelium rather well and we expect that this approach may be useful in the modeling of tissue transformations in other systems.

Animals↗

PubMed2002

WUSCHEL signaling functions in interregional communication during Arabidopsis ovule development.

Coordinating the behaviors of different cell populations is essential for multicellular development. One important example for this can be found in ovule development in higher plants. Ovules give rise to the gametophyte in the distal nucellus and form protective sporophytic organs from the underlying chalaza. We show that the WUSCHEL (WUS) homeobox gene provides a mechanism to coordinate these events. WUS is expressed in the nucellus and our loss- and gain-of-function analyses show that WUS is not only necessary but also sufficient for integument formation from the chalaza. WUS protein is retained in the nucellus, indicating that WUS activity in the nucellus generates a downstream signal that non-cell-autonomously regulates integument initiation in the chalaza. This signal appears to act locally, thus determining the position of organ formation from chalazal cells adjacent to the nucellus. Analysis of WUS and AINTEGUMENTA functions indicates that integument initiation requires inputs from different ovule regions. Together with previous findings for shoot and floral meristems, where WUS signaling establishes a stem cell niche, our results indicate that WUS defines a signaling mechanism that is used repeatedly during plant development in coordinating the behavior of adjacent cell groups.

Arabidopsis↗

PubMed1991

Bacterial swarming: an example of prokaryotic differentiation and multicellular behaviour.

Bacterial swarming involves the differentiation of vegetative cells into hyperflagellated swarm cells which undergo cycles of rapid and coordinated population migration across solid surfaces. Species capable of this simple form of developmental behaviour lie on the boundary between unicellular and multicellular organisms and provide processes for study which are not only of intrinsic interest but which are analogous to components of more complex eukaryotic systems. This review attempts to place current knowledge of bacterial swarming within the framework provided by more extensively studied forms of prokaryotic multicellular behaviour. It discusses the potential of swarming as a readily accessible model of differentiation and multicellular behaviour and describes evidence indicating that swarming differentiation plays an important role in bacterial virulence.

Bacterial Adhesion↗

PubMed2004

Dual functional regulators coordinate DNA replication and gene expression in proliferating cells.

Gene products for cell growth must meet the pace of DNA replication and vice versa during the cell division cycle, therefore coordination of DNA replication and gene expression is vital to proliferating cells. During development in multicellular organisms when rapid cell divisions must be accompanied by the expression of particular gene sets in differentiating tissues, this coordination is even more crucial. Undoubtedly, multiple strategies are used to ensure the coordination of gene expression and DNA replication. In this review, we focus on the strategy that uses dual functional factors to serve both the functions of replication initiator and transcription regulator. Classical examples are the dual functional replication initiator/transcription regulators, DnaA of E. coli and T antigen of SV40, which bind replication origins and regulate their own synthesis. Emerging examples in eukaryotes are the growth responsive transcription factor E2f, the MADS domain combinatorial transcription factor Mcm1, and a subunit of the MCM2-7 helicase, Mcm7.

Animals↗

PubMed1998

Reappraisal of the multicellular preparation for the in vitro physiopharmacological evaluation of myocardial performance.

In order to evaluate myocardial performance, single cardiomyocytes suffer from technical problems and from the fact that some basic functional properties vanish when one moves down the hierarchic scale from multicellularity to single cells. The isolated papillary muscle has at present proven to be superior to the isolated intact cardiomyocyte. A large number of major intra- and extracellular features required to describe myocardial performance can be derived from analyzing twitch contraction and relaxation in the multicellular isolated papillary muscle. In addition, the present paper illustrates the possibility to differentiate between effects of inotropic interventions on activating Ca2+ and Ca2+ sensitivity in multicellular preparations, from a grid analysis of isometric twitches in a coordinate system of peak rate of force development (+dF/dt; reflecting the time pattern of twitch contraction) versus time to half relaxation (tHR; reflecting the time pattern of twitch relaxation). The abundance of information about myocardial performance that can be derived from the easily accessible multicellular preparation reflects its physiological kinship with the intact ventricle.

Animals↗

PubMed1999

Selective cloning of cell surface proteins involved in organ development: epithelial glycoprotein is involved in normal epithelial differentiation.

Coordinating the activities of neighboring cells during development in multicellular organisms requires complex cellular interactions involving secreted, cell surface, and extracellular matrix components. Although most cloning efforts have concentrated on secreted molecules, recent work has emphasized the importance of membrane-bound molecules during development. To identify developmental genes, we raised antibodies to normal embryonic pancreatic epithelial cell surface proteins. These antibodies were characterized and used to clone the genes coding for the proteins by a panning strategy. Using this approach, we cloned the rat homologue of the mouse epithelial glycoprotein (EGP). Our immunohistochemistry data, describing the expression of EGP during rat development, as well as our in vitro data, looking at the effect of the anti-EGP antibody and the extracellular domain of EGP on embryonic pancreatic epithelial cell number and volume, strongly suggest a role for EGP during pancreatic development.

Amino Acid Sequence↗

PubMed2005

Expression profiling reveals functionally important genes and coordinately regulated signaling pathway genes during in vitro angiogenesis.

Angiogenesis is a complex multicellular process requiring the orchestration of many events including migration, alignment, proliferation, lumen formation, remodeling, and maturation. Such complexity indicates that not only individual genes but also entire signaling pathways will be crucial in angiogenesis. To define an angiogenic blueprint of regulated genes, we utilized our well-characterized three-dimensional collagen gel model of in vitro angiogenesis, in which the majority of cells synchronously progress through defined morphological stages culminating in the formation of capillary tubes. We developed a comprehensive three-tiered approach using microarray analysis, which allowed us to identify genes known to be involved in angiogenesis and genes hitherto unlinked to angiogenesis as well as novel genes and has proven especially useful for genes where the magnitude of change is small. Of interest is the ability to recognize complete signaling pathways that are regulated and genes clustering into ontological groups implicating the functional importance of particular processes. We have shown that consecutive members of the mitogen-activated protein kinase and leukemia inhibitory factor signaling pathways are altered at the mRNA level during in vitro angiogenesis. Thus, at least for the mitogen-activated protein kinase pathway, mRNA changes as well as the phosphorylation changes of these gene products may be important in the control of blood vessel morphogenesis. Furthermore, in this study, we demonstrated the power of virtual Northern blot analysis, as an alternative to quantitative RT-PCR, for measuring the magnitudes of differential gene expression.

Bayes Theorem↗

PubMed2000

Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating string/CDC25 proteolysis.

Morphogenesis and cell differentiation in multicellular organisms often require accurate control of cell divisions. We show that a novel cell cycle regulator, tribbles, is critical for this control during Drosophila development. During oogenesis, the level of tribbles affects the number of germ cell divisions as well as oocyte determination. The mesoderm anlage enters mitosis prematurely in tribbles mutant embryos, leading to gastrulation defects. We show that Tribbles acts by specifically inducing degradation of the CDC25 mitotic activators String and Twine via the proteosome pathway. By regulating CDC25, Tribbles serves to coordinate entry into mitosis with morphogenesis and cell fate determination.

Animals↗

PubMed1993

Identification and targeted gene disruption of cAR3, a cAMP receptor subtype expressed during multicellular stages of Dictyostelium development.

Extracellular cAMP acts through cell-surface receptors to coordinate the developmental program of Dictyostelium. A cAMP receptor (cAR1), which is expressed during early aggregation, has been cloned and sequenced previously. We have identified a new receptor subtype, cAR3, that has approximately 56% and 69% amino acid identity with cAR1 and cAR2, respectively. cAR1, cAR2, or cAR3 expressed from plasmid in growing Dictyostelium cells can be photoaffinity labeled with 8-N3[32P]cAMP and phosphorylated when stimulated with cAMP. cAR3 RNA was not present during growth but appeared during late aggregation. Its expression peaked at 9 hr and then fell to a reduced level that was maintained until culmination. The expression of cAR3 protein followed a similar pattern, but with a 3-hr lag, and reached a maximum at the mound stage. In contrast, cAR1 protein was expressed predominantly during early aggregation and at low levels during later stages. At their respective peaks of expression, there were approximately 5 x 10(3) cAR3 sites per cell compared with approximately 7 x 10(4) cAR2 sites per cell. The cAR3 gene was disrupted by homologous recombination in several different parental cell lines. Surprisingly, the car3- cell lines display no obvious phenotype.

Amino Acid Sequence↗

PubMed1988

What's new in the importance of receptors in pathology?

Highly organized multicellular organisms require a complex system of intercellular communication to coordinate the great variety of physiological functions. Major components of this system are the (i) signalling substances delivering the information and (ii) the corresponding cellular receptors recognizing the information and translating them to special intracellular organelles of the target cell. For the process of signal binding and transmission various types of receptor proteins are known playing a key role in the mutual understanding between cells. The present paper comprehends lectures on functions and deficiencies of the different types of cell receptors given during the Symposion on "Receptors in Pathology" during the 11th European Congress of Pathology. Each section is written under the personal responsibility of the author indicated.

Breast Diseases↗

PubMed2004

Spatiotemporal control of gene expression with pulse-generating networks.

One of the important challenges in the emerging field of synthetic biology is designing artificial networks that achieve coordinated behavior in cell communities. Here we present a synthetic multicellular bacterial system where receiver cells exhibit transient gene expression in response to a long-lasting signal from neighboring sender cells. The engineered sender cells synthesize an inducer, an acyl-homoserine lactone (AHL), which freely diffuses to spatially proximate receiver cells. The receiver cells contain a pulse-generator circuit that incorporates a feed-forward regulatory motif. The circuit responds to a long-lasting increase in the level of AHL by transiently activating, and then repressing, the expression of a GFP. Based on simulation models, we engineered variants of the pulse-generator circuit that exhibit different quantitative responses such as increased duration and intensity of the pulse. As shown by our models and experiments, the maximum amplitude and timing of the pulse depend not only on the final inducer concentration, but also on its rate of increase. The ability to differentiate between various rates of increase in inducer concentrations affords the system a unique spatiotemporal behavior for cells grown on solid media. Specifically, receiver cells can respond to communication from nearby sender cells while completely ignoring communication from senders cells further away, despite the fact that AHL concentrations eventually reach high levels everywhere. Because of the resemblance to naturally occurring feed-forward motifs, the pulse generator can serve as a model to improve our understanding of such systems.

Gene Expression Regulation↗

PubMedDate not supplied

[Homologous protein domains in superkingdoms Archaea, Bacteria, and Eukaryota and the problem of the origin of eukaryotes].

The distribution of protein domains was analyzed in superkingdoms Archaea, Bacteria, and Eukaryota. About a half of eukaryotic domains have prokaryotic origin. Many domains related to information processing in the nucleocytoplasm were inherited from archaea. Sets of domains associated with metabolism and regulatory and signaling systems were inherited from bacteria. Many signaling and regulatory domains common for bacteria and eukaryotes were responsible for the cellular interaction of bacteria with other components of the microbial community but were involved in coordination of the activity of eukaryotic organelles and cells in multicellular organisms. Many eukaryotic domains of bacterial origin could not originate from ancestral mitochondria and plastids but rather were adopted from other bacteria. An archaeon with the induced incorporation of alien genetic material could be the ancestor of the eukaryotic nucleocytoplasm.

Animals↗

PubMed1984

Common origin of linguistic and movement abilities.

We start with the view that the development of systems of symbols is rooted in the regulation of cellular processes and the behavior of unicellular animals. Animals would thereafter start to externalize these internal symbol systems, to coordinate movements with each other. We propose that the brains of multicellular animals can be understood as a continuing elaboration of the early chemical symbol systems of unicellular animals: the labile symbols of the unicellular animal are replaced by hormones, more stable chemical compounds, and nerves that are seen as more stable and more specific routes of activation; and brains developed layers of symbols such that the domain of a symbol is not a set of bodily processes but rather a set of brain processes. Human language is very much in the "style" of the rule-governed symbol manipulation required by all behaving animals, although unique in its complexity. We suggest that the essential question is not how humans have evolved symbolic and linguistic abilities from a primitive sensorimotor brain but rather how do symbols come to exist in biological systems and what is useful and necessary about a system of symbols for the coordination of action within animals and among animals.

Animals↗