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Results for “multicellular coordination”

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At least 253 records · Page 14Linked to original sources

PubMed2000

A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity.

Cellular asymmetry is critical for the development of multicellular organisms. Here we show that homologues of proteins necessary for asymmetric cell division in Caenorhabditis elegans associate with each other in mammalian cells and tissues. mPAR-3 and mPAR-6 exhibit similar expression patterns and subcellular distributions in the CNS and associate through their PDZ (PSD-95/Dlg/ZO-1) domains. mPAR-6 binds to Cdc42/Rac1 GTPases, and mPAR-3 and mPAR-6 bind independently to atypical protein kinase C (aPKC) isoforms. In vitro, mPAR-3 acts as a substrate and an inhibitor of aPKC. We conclude that mPAR-3 and mPAR-6 have a scaffolding function, coordinating the activities of several signalling proteins that are implicated in mammalian cell polarity.

Amino Acid Motifs↗

PubMed2000

Dictyostelium RasD is required for normal phototaxis, but not differentiation.

RasD, a Dictyostelium homolog of mammalian Ras, is maximally expressed during the multicellular stage of development. Normal Dictyostelium aggregates are phototactic and thermotactic, moving towards sources of light and heat with great sensitivity. We show that disruption of the gene for rasD causes a near-total loss of phototaxis and thermotaxis in mutant aggregates, without obvious effects on undirected movement. Previous experiments had suggested important roles for RasD in development and cell-type determination. Surprisingly, rasD(-) cells show no obvious changes in these processes. These cells represent a novel class of phototaxis mutant, and indicate a role for a Ras pathway in the connections between stimuli and coordinated cell movement.

Animals↗

PubMed2006

From fate to function: the Drosophila trachea and salivary gland as models for tubulogenesis.

Tube formation is a ubiquitous process required to sustain life in multicellular organisms. The tubular organs of adult mammals include the lungs, vasculature, digestive and excretory systems, as well as secretory organs such as the pancreas, salivary, prostate, and mammary glands. Other tissues, including the embryonic heart and neural tube, have requisite stages of tubular organization early in development. To learn the molecular and cellular basis of how epithelial cells are organized into tubular organs of various shapes and sizes, investigators have focused on the Drosophila trachea and salivary gland as model genetic systems for branched and unbranched tubes, respectively. Both organs begin as polarized epithelial placodes, which through coordinated cell shape changes, cell rearrangement, and cell migration form elongated tubes. Here, we discuss what has been discovered regarding the details of cell fate specification and tube formation in the two organs; these discoveries reveal significant conservation in the cellular and molecular events of tubulogenesis.

Animals↗

PubMed1999

Microarray analysis of Drosophila development during metamorphosis.

Metamorphosis is an integrated set of developmental processes controlled by a transcriptional hierarchy that coordinates the action of hundreds of genes. In order to identify and analyze the expression of these genes, high-density DNA microarrays containing several thousand Drosophila melanogaster gene sequences were constructed. Many differentially expressed genes can be assigned to developmental pathways known to be active during metamorphosis, whereas others can be assigned to pathways not previously associated with metamorphosis. Additionally, many genes of unknown function were identified that may be involved in the control and execution of metamorphosis. The utility of this genome-based approach is demonstrated for studying a set of complex biological processes in a multicellular organism.

Animals↗

PubMed2002

Regulation of protrusive and contractile cell-matrix contacts.

The extracellular matrix is vital for tissue organisation in multicellular organisms. Cells attach to the extracellular matrix at discrete points on the cell surface, termed cell-matrix contacts. In general molecular terms, these contacts are assembled from large multiprotein complexes. However, many forms of matrix contacts can be distinguished by microscopy or by biochemical criteria, and these fulfil a diverse range of roles associated with cell adhesion, guidance, migration, matrix assembly, differentiation and survival. Two major functional categories are the protrusive and contractile matrix contacts. I describe contexts for the formation of protrusive or contractile contacts and discuss recent information on the molecular processes by which these contacts are specified, coordinated and regulated at a cellular level.

Animals↗

PubMed2002

Extracellular cAMP inhibits proximal reabsorption: are plasma membrane cAMP receptors involved?

Glucagon binding to hepatocytes has been known for a long time to not only stimulate intracellular cAMP accumulation but also, intriguingly, induce a significant release of liver-borne cAMP in the blood. Recent experiments have shown that the well-documented but ill-understood natriuretic and phosphaturic actions of glucagon are actually mediated by this extracellular cAMP, which inhibits the reabsorption of sodium and phosphate in the renal proximal tubule. The existence of this "pancreato-hepatorenal cascade" indicates that proximal tubular reabsorption is permanently influenced by extracellular cAMP, the concentration of which is most probably largely dependent on the insulin-to-glucagon ratio. The possibility that renal cAMP receptors may be involved in this process is supported by the fact that cAMP has been shown to bind to brush-border membrane vesicles. In other cell types (i.e., adipocytes, erythrocytes, glial cells, cardiomyocytes), cAMP eggress and/or cAMP binding have also been shown to occur, suggesting additional paracrine effects of this nucleotide. Although not yet identified in mammals, cAMP receptors (cARs) are already well characterized in lower eukaryotes. The amoeba Dictyostelium discoideum expresses four different cARs during its development into a multicellular organism. cARs belong to the superfamily of seven transmembrane domain G protein-coupled receptors and exhibit a modest homology with the secretin receptor family (which includes PTH receptors). However, the existence of specific cAMP receptors in mammals remains to be demonstrated. Disturbances in the pancreato-hepatorenal cascade provide an adequate pathophysiological understanding of several unexplained observations, including the association of hyperinsulinemia and hypertension, the hepatorenal syndrome, and the hyperfiltration of diabetes mellitus. The observations reviewed in this paper show that cAMP should no longer be regarded only as an intracellular second messenger but also as a first messenger responsible for coordinated hepatorenal functions, and possibly for paracrine regulations in several other tissues.

Amino Acid Sequence↗

PubMed2006

The dynamic geometry of mass cell movements in animal morphogenesis.

There is an infinite number of interactions between morphogenetic processes of different time and space scales. How do these unfold in a regular series of mass morphogenetic movements to produce a basically simple and reproducible structure? I present a new morphogenetic concept -- the spatial unfolding (SU) of cell movements, whose definition rests on the correspondence between the continuous spatial series of cell shapes and the succession of changes in the shape of a single cell moving in an epithelial sheet whose shape is also subject to change. The change in the shape of moving cells is the only measure of their translocation both in space and time. The SU provides a morpho-dynamics description of mass cell movements which is completely independent of both an external coordinate system and external forces. The cell geometry of SU allows us to derive the future embryonic form from the actual one by a movement-shaping algorithm operating on the basis of positive and negative geometric feedbacks between the cell movement in the epithelial sheet plane and the epithelial sheet shaping, the feedback system providing a geometric alternative to Turing's self-organization via reaction-diffusion systems. Putting together histological, quantitative morphological and experimental data permits us to isolate four SU, each acting in morphogenesis as an irreducible whole, which seem to include all real examples of epithelial morphogenesis in multicellular animals, from Coelenterates to Chordates.

Animals↗

PubMed1992

Pattern and control in bacterial colony development.

As we learn more about bacterial life in the laboratory and in nature, we increasingly appreciate that they are highly sensitive and sophisticated organisms. One of the principal new insights has been the appreciation that bacteria are interactive and form organized, differentiated multicellular communities. Colonies produced on laboratory media by the standard research bacterium, Escherichia coli, are excellent examples. The organization of these colonies can be visualized in the microscope, by macrophotography, and by the use of special dyes and genetic engineering techniques to reveal patterns of differential gene expression. Observation of the dynamics of colony growth, and the response of colonies to experimental disruptions of normal development, indicate that control systems work to produce the regular patterns observed. The effects of obstacles and of other colonies on gene expression patterns indicate that non-linear responses to chemical gradients in the substrate play an important coordinating role in colony development.

Bacteria↗

PubMed1984

cAMP pulses coordinate morphogenetic movement during fruiting body formation of Dictyostelium minutum.

Aggregation in the primitive cellular slime mold Dictyostelium minutum proceeds by means of chemotaxis toward a continuously secreted folic acid analog [De Wit, R. J. W. & Konijn, T. M. (1983) Cell Differ. 12, 205-210]. The onset of culmination is marked by the appearance of concentric waves of cell movement on the aggregate surface. Culmination proceeds by the chemotactic attraction of amoebae to the center of wave propagation, which results in the accumulation of amoebae into a finger-like structure. Evidence is presented that the chemoattractant used during culmination is cAMP, which is secreted in pulses. The cells secrete cAMP themselves; cAMP receptors and phosphodiesterase activity appear on the cell surface just before the onset of culmination. Micromolar concentrations of externally applied cAMP induce disorientation of amoeboid movement at the onset of culmination. These observations are compatible with the hypothesis that the cAMP signaling system organizes multicellular development in both primitive and advanced cellular slime mold species. Advanced species such as Dictyostelium discoideum use this signaling system also in an earlier stage of development to organize the process of cell aggregation.

Journal Article↗

PubMed1984

An assay for pattern formation in dictyostelium discoideum using monoclonal antibodies, flow cytometry, and subsequent data analysis.

An assay for determining the proportions of prespore cells in a simple multicellular organism, the slug stage of Dictyostelium discoideum, was established using a prespore-specific monoclonal antibody and a fluorescence-activated cell sorter. Appropriate techniques for data analysis were developed. The effects of slug size and age were determined. Small slugs have a lower percentage of prespore cells than large slugs. The percentage of prespore cells increases and then decreases in slugs aged between a few hours and 9 days. Pronounced effects were observed on the size of cells in aging slugs. In particular unlabelled (mostly prestalk) cells were larger than prespore cells in young slugs, but after 6 days migration they became considerably smaller than prespore cells. The fact that all unlabelled cells were coordinately shifted in size, suggests that these cells (which comprise prestalk, prestalklike, and predisc cells) are related to each other.

Antibodies, Monoclonal↗

PubMed2006

Replication and translation of epigenetic information.

Most cells in multicellular organisms contain identical genetic information but differ in their epigenetic information. The latter is encoded at the molecular level by post-replicative methylation of certain DNA bases (in mammals 5-methyl cytosine at CpG sites) and multiple histone modifications in chromatin. In addition, higher-order chromatin structures are generated during differentiation, which might impact on genome expression and stability. The epigenetic information needs to be "translated" in order to define specific cell types with specific sets of active and inactive genes, collectively called the epigenome. Once established, the epigenome needs to be "replicated" at each cell division cycle, i.e., both genetic and epigenetic information have to be faithfully duplicated, which implies a tight coordination between the DNA replication machinery and epigenetic regulators. In this review, we focus on the molecules and mechanisms responsible for the replication and translation of DNA methylation in mammals as one of the central epigenetic marks.

Animals↗

PubMed2002

Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake.

In multicellular organisms, constituent cells depend on extracellular signals for growth, proliferation, and survival. When cells are withdrawn from growth factors, they undergo apoptosis. Expression of constitutively active forms of the serine/threonine kinase Akt/PKB can prevent apoptosis upon growth factor withdrawal. Akt-mediated survival depends in part on the maintenance of glucose metabolism, suggesting that reduced glucose utilization contributes to growth factor withdrawal-induced death. However, it is unclear how restricting access to extracellular glucose alone would lead to the metabolic collapse observed after growth factor withdrawal. We report herein that growth factor withdrawal results in the loss of surface transporters for not only glucose but also amino acids, low-density lipoprotein, and iron. This coordinated decline in transporters and receptors for extracellular molecules creates a catabolic state characterized by atrophy and a decline in the mitochondrial membrane potential. Activated forms of Akt maintained these transporters on the cell surface in the absence of growth factor through an mTOR-dependent mechanism. The mTOR inhibitor rapamycin diminished Akt-mediated increases in cell size, mitochondrial membrane potential, and cell survival. These results suggest that growth factors control cellular growth and survival by regulating cellular access to extracellular nutrients in part by modulating the activity of Akt and mTOR.

Amino Acids↗

PubMed2001

Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly.

Cellular polarization involves the generation of asymmetry along an intracellular axis. In a multicellular tissue, the asymmetry of individual cells must conform to the overlying architecture of the tissue. However, the mechanisms that couple cellular polarization to tissue morphogenesis are poorly understood. Here, we report that orientation of apical polarity in developing Madin-Darby canine kidney (MDCK) epithelial cysts requires the small GTPase Rac1 and the basement membrane component laminin. Dominant-negative Rac1 alters the supramolecular assembly of endogenous MDCK laminin and causes a striking inversion of apical polarity. Exogenous laminin is recruited to the surface of these cysts and rescues apical polarity. These findings implicate Rac1-mediated laminin assembly in apical pole orientation. By linking apical orientation to generation of the basement membrane, epithelial cells ensure the coordination of polarity with tissue architecture.

Actins↗

PubMed2002

Get a ligand, get a life: integrins, signaling and cell survival.

Programmed cell death is crucial for the development and maintenance of multicellular organisms. The decision to live, or to die, depends, at the cellular level, upon the cell's interaction with extracellular cues that trigger cell signaling pathways promoting survival or death. The extracellular matrix (ECM) influences the execution of the apoptotic program through the actions of adhesion receptors. Among these, integrins initiate a variety of downstream signaling events in response to ECM ligation. Integrins directly activate survival pathways via the PI 3-kinase and MAPK pathways and act as essential cofactors for their stimulation by growth factors. Conversely, elevated integrin expression in the absence of appropriate ligands, or in the presence of natural or synthetic antagonists, can promote apoptosis under otherwise permissive growth conditions. Integrins thus act in a crucial biosensory role, coordinating survival or death responses as a function of ECM composition. This dual function provides an elegant mechanism through which tissue-remodeling events may regulate cell death or survival in a temporal, ECM-governed manner.

Animals↗

PubMed1990

Defects in contact-stimulated gliding during aggregation by Myxococcus xanthus.

During development, Myxococcus xanthus cells glide toward foci of aggregation and produce compact multicellular mounds. We studied development in strains with defects in contact-stimulated gliding. Contact stimulation involves a mechanism influenced by contacts between neighboring cells which stimulates the gliding motility of single cells (Hodgkin and Kaiser, Proc. Natl. Acad. Sci. USA 74:2938-2942, 1977; Hodgkin and Kaiser, Mol. Gen. Genet. 171:167-176, 1979). Most mutants containing a mutation in a single gene affecting contact stimulation (cgl gene) were able to form foci of aggregation during development. However, the aggregates were diffuse, suggesting that contact stimulation is important for morphogenetic movements during aggregation. A mutant containing a mutation in the cglF3 gene showed a striking delay in aggregation, suggesting that the cglF3 gene affects a mechanism stimulating cells moving to foci or affects a mechanism for coordinating early cell behavior. Mutants containing the cglF3 mutation in combination with a cglB, cglC, cglE, or cglF1 mutation had severe defects in aggregation and failed to recover from the early delay. The severity of the defects in mutants containing two cgl mutations suggests that cgl genes are critical for development. We propose that cgl genes stimulate cell movement or control specific contacts between cells during aggregation.

Bacterial Outer Membrane Proteins↗

PubMed1998

The point of no return: mitochondria, caspases, and the commitment to cell death.

Apoptosis is a specialized mode of cell death finely regulated at the molecular level and conserved throughout evolution. In many instances during normal development or in order to maintain the homeostasis of a multicellular organism, a strategic intracellular program is initiated ensuring the fate of unwanted cells. Interference with this program has been implicated in many pathologies, particularly in cancer and autoimmune diseases. What is most important, from the organism's point of view, is that the dismissal of the outcast cells is accomplished serenely, i.e., the dying cells resign their existence without causing an inflammatory reaction. Therefore, the ability to manipulate the cell death machinery is an obvious goal of medical research. Here, we debate the idea of the point-of-no-return and propose models for the role of "initiator" and "executioner" caspases in the death program. We argue that, in many circumstances, the cells are committed to die before the execution phase of apoptosis starts. This commitment event is coordinated by the mitochondria and can be blocked by anti-apoptotic oncogenes.

Animals↗

PubMed2003

Regulation of F-actin-dependent processes by the Abl family of tyrosine kinases.

The F-actin cytoskeleton is a fundamental component of all eukaryotic cells. It provides force and stability and plays an integral role in a diverse array of cellular processes. The spatiotemporal regulation of F-actin dynamics is essential for proper biological output. The basic molecular machinery underlying the assembly and disassembly of filamentous actin is conserved in all eukaryotic cells. Additionally, protein tyrosine kinases, found only in multicellular eukaryotes, provide links between extracellular signals and F-actin-dependent cellular processes. Among the tyrosine kinases, c-Abl and its relative Arg are unique in binding directly to F-actin. Recent results have demonstrated a role for c-Abl in membrane ruffling, cell spreading, cell migration, and neurite extension in response to growth factor and extracellular matrix signals. c-Abl appears to regulate the assembly of F-actin polymers into different structures, depending on the extracellular signal. Interestingly, c-Abl contains nuclear import and export signals, and the nuclear c-Abl inhibits differentiation and promotes apoptosis in response to genotoxic stress. The modular structure and the nuclear-cytoplasmic shuttling of c-Abl suggest that it integrates multiple signals to coordinate F-actin dynamics with the cellular decision to differentiate or to die.

Actin Cytoskeleton↗

PubMed1997

Null mutations of the Dictyostelium cyclic nucleotide phosphodiesterase gene block chemotactic cell movement in developing aggregates.

Extracellular cAMP is a critical messenger in the multicellular development of the cellular slime mold Dictyostelium discoideum. The levels of cAMP are controlled by a cyclic nucleotide phosphodiesterase (PDE) that is secreted by the cells. The PDE gene (pdsA) is controlled by three promoters that permit expression during vegetative growth, during aggregation, and in prestalk cells of the older structures. Targeted disruption of the gene aborts development, and complementation with a modified pdsA restores development. Two distinct promoters must be used for full complementation, and an inhibitory domain of the PDE must be removed. We took advantage of newly isolated PDE-null cells and the natural chimerism of the organism to ask whether the absence of PDE affected individual cell behavior. PDE-null cells aggregated with isogenic wild-type cells in chimeric mixtures, but could not move in a coordinated manner in mounds. The wild-type cells move inward toward the center of the mound, leaving many of the PDE-null cells at the periphery of the aggregate. During the later stages of development, PDE-null cells in the chimera segregate to regions which correspond to the prestalk region and the rear of the slug. Participation in the prespore/spore population returns with the restoration of a modified pdsA to the null cells.

3',5'-Cyclic-AMP Phosphodiesterases↗