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Results for “multicellular coordination”

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PubMed2004

Cell cycling through development.

Regardless of the species, the development of a multicellular organism requires the precise execution of essential developmental processes including patterning, growth, proliferation and differentiation. The cell cycle, in addition to its role as coordinator of DNA replication and mitosis, is also a coordinator of developmental processes, and is a target of developmental signaling pathways. Perhaps because of its central role during development, the cell cycle mechanism, its regulation and its effects on developing tissues is remarkably complex. It was in this light that the Keystone meeting on the cell cycle and development at Snowbird, Utah in January 2004 was held.

Aging↗

PubMed2004

Kinetics of the neuroinflammation-oxidative stress correlation in rat brain following the injection of fibrillar amyloid-beta onto the hippocampus in vivo.

The purpose of this study was to describe-following the injection of a single intracerebral dose of fibrillar amyloid-beta(1-40) in vivo-some correlations between proinflammatory cytokines and oxidative stress indicators in function of time, as well as how these variables fit in a regression model. We found a positive, significant correlation between interleukin (IL)-1beta or IL-6 and the activity of the glutathione peroxidase enzyme (GSH-Px), but IL-1beta or IL-6 maintained a strong, negative correlation with the lipid peroxidation (LPO). The first 12 h marked a positive correlation between IL-6 and tumor necrosis factor-alpha (TNF-alpha), but starting from the 36 h, this relationship became negative. We found also particular patterns of behavior through the time for IL-1beta, nitrites and IL-6, with parallel or sequential interrelationships. Results shows clearly that, in vivo, the fibrillar amyloid-beta (Abeta) disrupts the oxidative balance and initiate a proinflammatory response, which in turn feeds the oxidative imbalance in a coordinated, sequential way. This work contributes to our understanding of the positive feedbacks, focusing the "cytokine cycle" along with the oxidative stress mediators in a complex, multicellular, and interactive environment.

Amyloid beta-Peptides↗

PubMed2006

Rethinking 'secondary' metabolism: physiological roles for phenazine antibiotics.

Microorganisms exist in the environment as multicellular communities that face the challenge of surviving under nutrient-limited conditions. Chemical communication is an essential part of the way in which these populations coordinate their behavior, and there has been an explosion of understanding in recent years regarding how this is accomplished. Much less, however, is understood about the way these communities sustain their metabolism. Bacteria of the genus Pseudomonas are ubiquitous, and are distinguished by their production of colorful secondary metabolites called phenazines. In this article, we suggest that phenazines, which are produced under conditions of high cell density and nutrient limitation, may be important for the persistence of pseudomonads in the environment.

Animals↗

PubMed2004

Femtomolar sensitivity of a NO sensor from Clostridium botulinum.

Nitric oxide (NO) is extremely toxic to Clostridium botulinum, but its molecular targets are unknown. Here, we identify a heme protein sensor (SONO) that displays femtomolar affinity for NO. The crystal structure of the SONO heme domain reveals a previously undescribed fold and a strategically placed tyrosine residue that modulates heme-nitrosyl coordination. Furthermore, the domain architecture of a SONO ortholog cloned from Chlamydomonas reinhardtii indicates that NO signaling through cyclic guanosine monophosphate arose before the origin of multicellular eukaryotes. Our findings have broad implications for understanding bacterial responses to NO, as well as for the activation of mammalian NO-sensitive guanylyl cyclase.

Aerobiosis↗

PubMed2004

Multicellular computer simulation of morphogenesis: blastocoel roof thinning and matrix assembly in Xenopus laevis.

In the blastocoel roof (BCR) of the Xenopus laevis embryo, epibolic movements are driven by the radial intercalation of deep cell layers and the coordinate spreading of the overlying superficial cell layer. Thinning of the lateral margins of the BCR by radial intercalation requires fibronectin (FN), which is produced and assembled into fibrils by the inner deep cell layer of the BCR. A cellular automata (CA) computer model was developed to analyze the spatial and temporal movements of BCR cells during epiboly. Simulation parameters were defined based on published data and independent results detailing initial tissue geometry, cell numbers, cell intercalation rates, and migration rates. Hypotheses regarding differential cell adhesion and FN assembly were also considered in setting system parameters. A 2-dimensional model simulation was developed that predicts BCR thinning time of 4.8 h, which closely approximates the time required for the completion of gastrulation in vivo. Additionally, the model predicts a temporal increase in FN matrix assembly that parallels fibrillogenesis in the embryo. The model is capable of independent predictions of cell rearrangements during epiboly, and here was used to predict successfully the lateral dispersion of a patch of cells implanted in the BCR, and increased assembly of FN matrix following inhibition of radial intercalation by N-cadherin over-expression.

Animals↗

PubMed2001

Intercellular mechanotransduction: cellular circuits that coordinate tissue responses to mechanical loading.

Physical forces play an important role in modulating cell function and shaping tissue structure. Mechanotransduction, the process by which cells transduce physical force-induced signals into biochemical responses, is critical for mediating adaptations to mechanical loading in connective tissues. While much is known about mechanotransduction in cells involving forces delivered through extracellular matrix proteins and integrins, there is limited understanding of how mechanical signals are propagated through the interconnected cellular networks found in tissues and organs. We propose that intercellular mechanotransduction is a critical component for achieving coordinated remodeling responses to force application in connective tissues. We examine here recent evidence on different pathways of intercellular mechanotransduction and suggest a general model for how multicellular structures respond to mechanical loading as an integrated unit.

Adaptation, Physiological↗

PubMed2006

Functional analysis of luxS in the probiotic strain Lactobacillus rhamnosus GG reveals a central metabolic role important for growth and biofilm formation.

Quorum sensing is involved in the regulation of multicellular behavior through communication via small molecules. Given the high number and diversity of the gastrointestinal microbiota, it is postulated that members of this community communicate to coordinate a variety of adaptive processes. AI-2 is suggested to be a universal bacterial signaling molecule synthesized by the LuxS enzyme, which forms an integral part of the activated methyl cycle. We have previously reported that the well-documented probiotic strain Lactobacillus rhamnosus GG, a human isolate, produces AI-2-like molecules. In this study, we identified the luxS homologue of L. rhamnosus GG. luxS seems to be located in an operon with a yxjH gene encoding a putative cobalamin-independent methionine synthase. In silico analysis revealed a methionine-specific T box in the leader sequence of the putative yxjH-luxS operon. However, transcriptional analysis showed that luxS is expressed mainly as a monocistronic transcript. Construction of a luxS knockout mutant confirmed that the luxS gene is responsible for AI-2 production in L. rhamnosus GG. However, this mutation also resulted in pleiotropic effects on the growth of this fastidious strain. Cysteine, pantothenate, folic acid, and biotin could partially complement growth, suggesting a central metabolic role for luxS in L. rhamnosus GG. Interestingly, the luxS mutant also showed a defect in monospecies biofilm formation. Experiments with chemically synthesized (S)-4,5-dihydroxy-2,3-pentanedione, coculture with the wild type, and nutritional complementation suggested that the main cause of this defect has a metabolic nature. Moreover, our data indicate that suppressor mutations are likely to occur in luxS mutants of L. rhamnosus GG. Therefore, results of luxS-related studies should be carefully interpreted.

Bacterial Proteins↗

PubMed2002

Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice.

Apoptosis, a molecularly regulated form of cell death, is essential for the normal functioning and homeostasis of most multicellular organisms, and can be induced by a range of environmental, physical, and chemical stresses. As the cellular decision to live or to die is made by the coordinated action and balancing of many different pro- and antiapoptotic factors, defects in control of this coordination and balance may contribute to a variety of human diseases, including cancer and autoimmune and neurodegenerative conditions. In recent years, multiple factors associated with the execution of apoptosis, such as caspases and Bcl-2 family members, have been discovered and their complicated signaling and molecular interactions have been demonstrated; however, the precise mechanistic basis for intracellular and/or extracellular stress-induced apoptosis remains to be fully characterized. Protein kinases contribute to regulation of life and death decisions made in response to various stress signals, and the actions of pro- and antiapoptotic factors are often affected by modulation of the phosphorylation status of key elements in the execution of apoptosis. Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein (MAP) kinase kinase kinase family, which activates both the MKK4/MKK7-JNK and MKK3/MKK6-p38 MAP kinase pathways and constitutes a pivotal signaling pathway in various types of stress-induced apoptosis. We have recently shown through ASK1 gene ablation in mice that ASK1 plays essential roles in oxidative stress- and endoplasmic reticulum (ER) stress-induced apoptosis. These stresses are closely linked to physiological phenomena in the control of cell fate, and the resultant apoptosis is implicated in the pathophysiology of a broad range of human diseases. This article reviews our new findings on the physiological roles of ASK1-mediated signal transduction in stress responses and the molecular mechanisms by which ASK1 determines cell fate such as survival, differentiation, or apoptosis, with special focus on the regulatory mechanisms of ASK1-mediated apoptosis induced by oxidative stress and ER stress.

Animals↗

PubMed2001

p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding.

Our environment contains physical, chemical and pathological agents that challenge the integrity of our DNA. In addition to DNA repair, higher multicellular organisms have evolved multiple pathways of response to damage including programmed cell death-apoptosis. The p53 protein appears to sense multiple types of DNA damage and coordinate with multiple options for cellular response. The p53 protein activities depend upon its DNA binding. Specific p53 protein post-translational modifications are required for efficient sequence-specific binding and transcriptional activities. Non-sequence-specific DNA binding may involve a wide spectrum of p53 proteins and predominate as DNA damage is more severe or p53 protein is more highly induced. p53 protein is not strictly required for DNA damage sensing and repair. Rather, p53 protein may govern an apoptosis checkpoint through competition with DNA repair proteins for non-sequence-specific binding to exposed single-stranded regions in the DNA duplex. This model provides a framework for testing mechanisms of p53-mediated apoptosis dependent upon the p53 protein modification state, the level of p53 protein accumulation, the level of DNA damage and the capacity of the damaged cell to repair.

Animals↗

PubMed1999

Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation.

Oscillations of cytosolic free calcium levels have been shown to influence gene regulation and cell differentiation in a variety of model systems. Intercellular calcium waves thus present a plausible mechanism for coordinating cellular processes during embryogenesis. Herein we report use of aequorin and a photon imaging microscope to directly observe a rhythmic series of intercellular calcium waves that circumnavigate zebrafish embryos over a 10-h period during gastrulation and axial segmentation. These waves first appeared at about 65% epiboly and continued to arise every 5-10 min up to at least the 16-somite stage. The waves originated from loci of high calcium activity bordering the blastoderm margin. Several initiating loci were active early in the wave series, whereas later a dorsal marginal midline locus predominated. On completion of epiboly, the dorsal locus was incorporated into the developing tail bud and continued to generate calcium waves. The locations and timing at which calcium dynamics are most active appear to correspond closely to embryonic cellular and syncytial sites of known morphogenetic importance. The observations suggest that a panembryonic calcium signaling system operating in a clock-like fashion might play a role during vertebrate axial patterning.

Aequorin↗

PubMed1994

Mechanisms and function of intercellular calcium signaling.

Intercellular Ca2+ waves initiated by mechanical or chemical stimuli propagate between cells via gap junctions. The ability of a wide diversity of cells to display intercellular Ca2+ waves suggests that these Ca2+ waves may represent a general mechanism by which cells communicate. Although Ca2+ may permeate gap junctions, the intercellular movement of Ca2+ is not essential for the propagation of Ca2+ waves. The messenger that moves from one cell to the next through gap junctions appears to be IP3 and a regenerative mechanism for IP3 may be required to effect multicellular communication. Extracellularly mediated Ca2+ signaling also exists and this could be employed to supplement or replace gap junctional communication. The function of intercellular Ca2+ waves may be the coordination of cooperative cellular responses to local stimuli.

Animals↗

PubMed2003

Visualization of Proteus mirabilis morphotypes in the urinary tract: the elongated swarmer cell is rarely observed in ascending urinary tract infection.

Proteus mirabilis, a common cause of nosocomial and catheter-associated urinary tract infection, colonizes the bladder and ascends the ureters to the proximal tubules of the kidneys, leading to the development of acute pyelonephritis. P. mirabilis is capable of swarming, a form of multicellular behavior in which bacteria differentiate from the short rod typical of members of the family Enterobacteriaceae, termed the swimmer cell, into hyperflagellated elongated bacteria capable of rapid and coordinated population migration across surfaces, called the swarmer cell. There has been considerable debate as to which morphotype predominates during urinary tract infection. P. mirabilis(pBAC001), which expresses green fluorescent protein in both swimming and swarming morphotypes, was constructed to quantify the prevalence of each morphotype in ascending urinary tract infection. Transurethral inoculation of P. mirabilis(pBAC001) resulted in ascending urinary tract infection and kidney pathology in mice examined at both 2 and 4 days postinoculation. Using confocal microscopy, we were able to investigate the morphotypes of the bacteria in the urinary tract. Of 5,087 bacteria measured in bladders, ureters, and kidneys, only 7 (0.14%) were identified as swarmers. MR/P fimbria expression, which correlates with the swimmer phenotype, is prevalent on bacteria in the ureters and bladder. We conclude that, by far, the predominant morphotype present in the urinary tract during ascending infection is the short rod-the swimmer cell.

Animals↗

PubMed1999

The Embryonics Project: a machine made of artificial cells.

It is possible to trace the origins of biological inspiration in the design of electronic circuits to the very dawn of the field of computer engineering, with the work of John von Neumann in the 1940s. To his brilliance we owe not only the first methodical attempts to define the electronic equivalents of many fundamental biological process, but also the development of the first self-replicating computing machines. Unfortunately, the electronic technology of the time would not allow a physical realization of von Neumann's machines, and it was not until the introduction of new programmable circuits in the 1980s that the field of bio-inspired machines gained new momentum. In this article, we describe the Embryonics (embryonic electronics) Project, an attempt to draw inspiration from the ontogenetic processes that determine the growth of multicellular organisms in the design of new, massively parallel arrays of processors (the artificial cells). Our cells are simple processors, all based on an identical hardware structure and all containing the same program (our artificial genome), but executing different parts of the genome depending on their spatial coordinates within the array. As in living beings, the presence of the genome in every cell allows the introduction of features such as self-replication and self-repair (cicatrization). In addition, the cells are implemented using an array of programmable elements (the artificial molecules), which allows their structure to be adapted to a given application. Through the parallel operation of many of these simple processors, we hope to realize highly complex systems, the equivalent of multicellular organisms in the natural world.

Animals↗

PubMed2003

Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium.

The two major theories of cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, view tumor cell adhesion to blood vessel endothelia and cancer cell aggregation as corresponding key components of the metastatic process. Here, we demonstrate in vitro, ex vivo, and in vivo that metastatic breast and prostate carcinoma cells form multicellular homotypic aggregates at the sites of their primary attachment to the endothelium. Our results suggest that metastatic cell heterotypic adhesion to the microvascular endothelium and homotypic aggregation represent two coordinated subsequent steps of the metastatic cascade mediated largely by similar molecular mechanisms, specifically by interactions of tumor-associated Thomsen-Friedenreich glycoantigen with the beta-galactoside-binding protein, galectin-3. In addition to inhibiting neoplastic cell adhesion to the endothelium and homotypic aggregation, disrupting this line of intercellular communication using synthetic Thomsen-Friedenreich antigen masking and Thomsen-Friedenreich antigen mimicking compounds greatly affects cancer cell clonogenic survival and growth as well. Thus, beta-galactoside-mediated intravascular heterotypic and homotypic tumor cell adhesive interactions at the sites of a primary attachment to the microvascular endothelium could play an important role during early stages of hematogenous cancer metastasis.

Animals↗

PubMed2002

Cripto, a multifunctional partner in signaling: molecular forms and activities.

Within a multicellular organism, communication between cells is essential during development to ensure proper execution of cell migration, cell fate decisions, and differentiation events. It is also essential in the adult for the coordination of many physiological functions. Cell-to-cell communications often rely on the interaction of cell surface receptors with soluble or membrane-bound ligands. Receptors or ligands may interact with additional partners to trigger specific signaling cascades inside the cell. In most cases, partners act in a specific configuration, either as a diffusible "co-ligand" or a membrane-bound co-receptor. Here, we examine the case of Cripto, a signaling molecule that has prominent functions during vertebrate development. Conflicting results have suggested that Cripto has the unusual capacity to act both as a secreted ligand and as a cell surface component to control a single signaling pathway. Here, we review the recent experiments that attempt to reconcile those results. Furthermore, three reports have described the fact that Cripto is modified by the addition of sugar residues, including a rare case of fucosylation. These modifications are essential for Cripto function, suggesting that, as is the case for other key developmental or physiological regulators such as Notch or selectins, the activity of Cripto may be controlled by the extent of its glycosylation or fucosylation (or both).

Animals↗

PubMed1999

Extensive gene duplication in the early evolution of animals before the parazoan-eumetazoan split demonstrated by G proteins and protein tyrosine kinases from sponge and hydra.

To know whether genes involved in cell-cell communication typical of multicellular animals dramatically increased in concert with the Cambrian explosion, the rapid evolutionary burst in the major groups of animals, and whether these genes exist in the sponge lacking cell cohesiveness and coordination typical of eumetazoans, we have carried out cloning of the G-protein alpha subunit (Galpha) and the protein tyrosine kinase (PTK) cDNAs from Ephydatia fluviatilis (freshwater sponge) and Hydra magnipapillata strain 105 (hydra). We obtained 13 Galpha and 20 PTK cDNAs. Generally animal gene families diverged first by gene duplication (subtype duplication) that gave rise to diverse subtypes with different primary functions, followed by further gene duplication in the same subtype (isoform duplication) that gave rise to isoform genes with virtually identical function. Phylogenetic trees of Galpha and PTK families including cDNAs from sponge and hydra revealed that most of the present-day subtypes had been established in the very early evolution of animals before the parazoan-eumetazoan split, the earliest branching among the extant animal phyla, by extensive subtype duplication: for PTK and Galpha families, 23 and 9 subtype duplications were observed in the early stage before the parazoan-eumetazoan split, respectively, and after that split, only 2 and 1 subtype duplications were found, respectively. After the separation from arthropods, vertebrates underwent frequent isoform duplications before the fish-tetrapod split. Furthermore, rapid amino acid changes appear to have occurred in concert with the extensive subtype duplication and isoform duplication. Thus the pattern of gene diversification during animal evolution might be characterized by bursts of gene duplication interrupted by considerably long periods of silence, instead of proceeding gradually, and there might be no direct link between the Cambrian explosion and the extensive gene duplication that generated diverse functions (subtypes) of these families.

Amino Acid Substitution↗

PubMed2004

eor-1 and eor-2 are required for cell-specific apoptotic death in C. elegans.

Programmed cell death occurs in every multicellular organism and in diverse cell types yet the genetic controls that define which cells will live and which will die remain poorly understood. During development of the nematode Caenorhabditis elegans, the coordinated activity of four gene products, EGL-1, CED-9, CED-4 and CED-3, results in the death of essentially all cells fated to die. To identify novel upstream components of the cell death pathway, we performed a genetic screen for mutations that abolish the death of the hermaphrodite-specific neurons (HSNs), a homologous pair of cells required for egg-laying in the hermaphrodite. We identified and cloned the genes, eor-1 and eor-2, which are required to specify the fate of cell death in male HSNs. In addition to defects in HSN death, mutation of either gene leads to defects in coordinated movement, neuronal migration, male tail development, and viability; all consistent with abnormal neuronal differentiation. eor-1 encodes a putative transcription factor related to the human oncogene PLZF. eor-2 encodes a novel but conserved protein. We propose that eor-1 and eor-2 function together throughout the nervous system to promote terminal differentiation of neurons and function specifically in male HSNs to promote apoptotic death of the HSNs.

Amino Acid Sequence↗

PubMed2006

Flows driven by flagella of multicellular organisms enhance long-range molecular transport.

Evolution from unicellular organisms to larger multicellular ones requires matching their needs to the rate of exchange of molecular nutrients with the environment. This logistic problem poses a severe constraint on development. For organisms whose body plan is a spherical shell, such as the volvocine green algae, the current (molecules per second) of needed nutrients grows quadratically with radius, whereas the rate at which diffusion alone exchanges molecules grows linearly, leading to a bottleneck radius beyond which the diffusive current cannot meet metabolic demands. By using Volvox carteri, we examine the role that advection of fluid by the coordinated beating of surface-mounted flagella plays in enhancing nutrient uptake and show that it generates a boundary layer of concentration of the diffusing solute. That concentration gradient produces an exchange rate that is quadratic in the radius, as required, thus circumventing the bottleneck and facilitating evolutionary transitions to multicellularity and germ-soma differentiation in the volvocalean green algae.

Animals↗