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Results for “multicellular coordination”

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PubMed2006

Developmental timing in Dictyostelium is regulated by the Set1 histone methyltransferase.

Histone-modifying enzymes have enormous potential as regulators of the large-scale changes in gene expression occurring during differentiation. It is unclear how different combinations of histone modification coordinate regimes of transcription during development. We show that different methylation states of lysine 4 of histone H3 (H3K4) mark distinct developmental phases of the simple eukaryote, Dictyostelium. We demonstrate that the enzyme responsible for all mono, di and tri-methylation of H3K4 is the Dictyostelium homolog of the Set1 histone methyltransferase. In the absence of Set1, cells display unusually rapid development, characterized by precocious aggregation of amoebae into multicellular aggregates. Early differentiation markers are abundantly expressed in growing set1 cells, indicating the differentiation program is ectopically activated during growth. This phenotype is caused specifically by the loss of Set1 catalytic activity. Set1 mutants induce premature differentiation in wild-type cells, indicating Set1 regulates production of an extra-cellular factor required for the correct perception of growth conditions. Microarray analysis of the set1 mutants reveals genomic clustering of mis-expressed genes, suggesting a requirement for Set1 in the regulation of chromatin-mediated events at gene clusters.

Amino Acid Sequence↗

PubMed2001

Tobamoviral movement protein transiently expressed in a single epidermal cell functions beyond multiple plasmodesmata and spreads multicellularly in an infection-coupled manner.

Cell-to-cell movement of a plant virus requires expression of the movement protein (MP). It has not been fully elucidated, however, how the MP functions in primary infected cells. With the use of a microprojectile bombardment-mediated DNA infection system for Tomato mosaic virus (ToMV), we found that the cotransfected ToMV MP gene exerts its effects in the initially infected cells and in their surrounding cells to achieve multicellular spread of movement-defective ToMV. Five other tobamoviral MPs examined also transcomplemented the movement-defective phenotype of ToMV, but the Cucumber mosaic virus 3a MP did not. Together with the cell-to-cell movement of the mutant virus, a fusion between the MP and an enhanced green fluorescent protein variant (EGFP) expressed in trans was distributed multicellularly and localized primarily in plasmodesmata between infected cells. In contrast, in noninfected sites the MP-EGFP fusion accumulated predominantly inside the bombarded cells as irregularly shaped aggregates, and only a minute amount of the fusion was found in plasmodesmata. Thus, the behavior of ToMV MP is greatly modulated in the presence of a replicating virus and it is highly likely that the MP spreads in the infection sites, coordinating with the cell-to-cell movement of the viral genome.

Amino Acid Sequence↗

PubMed2006

The role of chromatin structure in regulating stress-induced transcription in Saccharomyces cerevisiae.

All cells, whether free-living or part of a multicellular organism, must contend with a variety of environmental fluctuations that can be harmful or lethal to the cell. Cells exposed to different kinds of environmental stress rapidly alter gene transcription, resulting in the immediate downregulation of housekeeping genes, while crucial stress-responsive transcription is drastically increased. Common cis-acting elements within many stress-induced promoters, such as stress response elements and heat shock elements, allow for coordinated expression in response to many different stresses. However, specific promoter architectures, i.e., specific combinations of high- and low-affinity stress-responsive cis elements embedded in a particular chromatin environment, allow for unique expression patterns that are responsive to the individual type and degree of stress. The coordination of transcriptional stress responses and the role that chromatin structure plays in the regulation and kinetics of such responses is discussed. The interplay among global and gene-specific stress responses is illustrated using the constitutive and stress-induced transcriptional regulation of HSP82 as a model. This review also investigates evidence suggesting that stress-induced transcription is globally synchronized with the stress-induced repression of housekeeping gene via 2 distinct mechanisms of facilitating the binding of TATA-binding protein (TBP): TFIID and SAGA-mediated TBP binding.

Chromatin↗

PubMed2001

Primary and secondary plasmodesmata: structure, origin, and functioning.

In the multicellular organisms of higher plants, plasmodesmata provide pathways for intimate symplasmic communication between neighboring cells. The arguments summarized in the present review demonstrate that plasmodesmata are diverse and highly dynamic structures. Differences in the plasmodesmal origin and modifications of the plasmodesmal structure and functioning at the various cell interfaces are the basic means which give rise to a complicated and flexibile symplasmic network. This complex communication system is discussed to serve a significant role in the coordinated development and in the concerted physiological functioning of the cells within the plant tissues, organs, and organisms.

Cell Communication↗

PubMed2003

The Nuclear Factor I (NFI) gene family in mammary gland development and function.

Mammary gland development and function require the coordinated spatial and temporal expression of a large fraction of the mammalian genome. A number of site-specific transcription factors are essential to achieve the appropriate growth, branching, expansion, and involution of the mammary gland throughout early postnatal development and the lactation cycle. One family of transcription factors proposed to play a major role in the mammary gland is encoded by the Nuclear Factor I (NFI) genes. The NFI gene family is found only in multicellular animals, with single genes being present in flies and worms and four genes in vertebrates. While the NFI family expanded and diversified prior to the evolution of the mammary gland, it is clear that several mammary-gland specific genes are regulated by NFI proteins. Here we address the structure and evolution of the NFI gene family and examine the role of the NFI transcription factors in the expression of mammary-gland specific proteins, including whey acidic protein and carboxyl ester lipase. We discuss current data showing that unique NFI proteins are expressed during lactation and involution and suggest that the NFI gene family likely has multiple important functions throughout mammary gland development.

Animals↗

PubMed2005

From oogenesis through gastrulation: developmental regulation of apoptosis.

Apoptosis is a mechanism employed by multicellular organisms throughout development as a means of eliminating damaged or otherwise unwanted cells. From oogenesis through fertilization and gastrulation, organisms use an array of cell- and tissue-specific mechanisms to regulate the apoptotic program in response to stress or developmental cues. Since cell death regulation is tightly interwoven with cell cycle and checkpoint controls, and embryos of the fly, fish and frog exhibit unique embryonic cell cycle regulation, it is of great interest to understand how early embryos coordinate these cellular functions.

Animals↗

PubMed2006

Cell cycle regulation in the developing lens.

Regulation of cell proliferation is a critical aspect of the development of multicellular organisms. The ocular lens is an excellent model system in which to unravel the mechanisms controlling cell proliferation during development. In recent years, several cell cycle regulators have been shown to be essential for maintaining normal patterns of lens cell proliferation. Additionally, many growth factor signaling pathways and cell adhesion factors have been shown to have the capacity to regulate lens cell proliferation. Given this complexity, understanding the cross talk between these many signaling pathways and how they are coordinated are important directions for the future.

Animals↗

PubMed1993

Plasmodesmata: the intercellular organelles of green plants.

Cytokinesis in higher plants results in the incomplete separation of daughter cells, due to the formation of special plasma-membrane-lined cytoplasmic bridges, called plasmodesmata. Within the green algae, these structures coordinate biochemical and physiological processes by facilitating the cell-to-cell diffusion of simple metabolites and ions. Until recently, most plant biologists thought that plasmodesmata perform a similar function in higher plants. However, it is now known that the more structurally advanced plasmodesmata of higher plants can also traffic macromolecules, including proteins and nucleic acids. These findings give new insights into how green plants evolved the ability to orchestrate their developmental and physiological processes in a supracellular rather than a multicellular manner.

Journal Article↗

PubMed2003

A new genetic locus controlling growth and proliferation in Drosophila melanogaster.

Multicellular organisms grow through both proliferation and growth of their individual cells. We have conducted a P-element-based misexpression screen for genes whose upregulation alters wing disc growth during development. One particular group of four P elements, all inserted at cytological location 61C7-8, exhibited specific overgrowth upon misexpression in proliferating imaginal tissues. Clonal analysis revealed that upon misexpression, cell number was increased but cell size was not affected, indicating that cell growth and proliferation were induced in a coordinate manner. Loss of function at the locus produced small flies with reduced cell number, consistent with the presence of a gene encoding a positive growth regulator. We characterized a new transcription unit initiating in a region adjacent to the P insertions, which generated a complex series of polyadenylated transcripts. Although these RNAs were induced in response to misexpression, none was sufficient by itself to recapitulate overgrowth when overexpressed. This suggested either that a particular combination of these transcripts was necessary or that other sequences are involved.

Animals↗

PubMed2006

mTOR, Akt, S6 kinases and the control of skeletal muscle growth.

In multicellular organisms, growth and metabolism are controlled by extracellular signals, such as insulin and insulin-like growth factors (IGFs). Depending on nutrient availability, these factors regulate cell number, cell size, storage of lipids, proteins and sugars. Here we will review recent literature on the intracellular signal transduction pathways regulating the anabolic responses in skeletal muscles. Emphasis will be put on three serine/threonine kinases, mTOR, Akt and S6 Kinase (S6K), and their role in the integration of environmental cues and the coordination of muscle growth.

Adaptor Proteins, Signal Transducing↗

PubMed1999

The significance of platelet-derived growth factors for proliferation of vascular smooth muscle cells.

Platelets are important in acute thrombotic occlusion of injured vessels, e.g., subsequent to angioplasty. In contrast to these acute events of thrombus formation, much less is known about the significance of platelets for the control of smooth muscle cell (SMC) proliferation. A body of experimental and clinical evidence indicates an involvement of platelets in the pathology of atherosclerosis and restenosis. However, the precise role of platelet-derived growth factors for SMC proliferation in atherosclerotic and restenotic vessels is not clear and many questions remain unresolved. Platelet-dependent SMC mitogenesis is determined by a coordinate action of several classes of mitogenic factors which are either released from storage pools or generated upon platelet activation. Although platelet-derived growth factor (PDGF) is considered to be the most important platelet mitogen it is very likely that yet unknown factors and mechanisms are involved. Differential (stimulatory or inhibitory) effects on SMC growth and differentiation have been reported for different platelet-derived growth factors. Thus, for the overall response, complex interactions between multiple factors need to be considered. In addition, multicellular interactions, e.g., between platelets and endothelial cells may modulate the effects of platelet-derived factors on SMC mitogenesis. Taken together, the mechanisms of platelet-dependent SMC proliferation need to be reevaluated. The assessment of the precise role of platelet mitogens in the complex proliferative repair mechanisms of an injured vessel wall clearly requires further studies.

Journal Article↗

PubMed2003

Modelling of Dictyostelium discoideum slug migration.

The development of most multicellular organisms involves differential movement of cells resulting in the formation of tissues. The principles governing these movements are poorly understood. One exception is the formation of the slug in the social amoebae Dictyostelium discoideum. The slug forms by the chemotactic aggregation of up to 10(5) starving cells, it is motile and migrates in response to light and temperature gradients to the surface of the soil to form a fruiting body consisting of a stalk supporting a spore head. Slug migration and behaviour result from coordinated chemotactic movement of the individual cells in the slug. Waves of a chemoattractant, most likely cAMP, are periodically initiated in the tip of the slug and propagate towards the back of the slug resulting in periodic forward movement of individual cells as well as the whole slug. Here we develop a model to investigate how wave propagation and cell movement interacts to result in migration and shape changes of the slug. The slug tissue is modelled as an incompressible liquid, in which waves of chemoattractant are generated in an excitable manner. The liquid is "active", i.e. it is able to generate body forces in response to the gradients of the chemoattractant. These forces lead to the formation of flows (representing chemotactically moving cells) and result in slug movement and shape changes. The model provides a theoretical framework for the understanding of the interactions between cell-cell signalling and cell movement, which govern slug behaviour and tissue morphogenesis.

Animals↗

PubMed1990

Intracellular signal transduction pathways in sponges.

Sponges are the lowest multicellular eukaryotic organisms. Due to the relatively low specialization, and concomitantly the high differentiation and dedifferentiation potency of their cells, the sponge cell system has proven to be a useful model to study the mechanism of cell-cell adhesion on molecular levels. Results of detailed biochemical and cell biological studies with the main cell adhesion molecules, the aggregation factor (AF) and the aggregation receptor, led to the formation of the modulation theory of cell adhesion. The events of cell adhesion are contigent on a multiplicity of precisely coordinated intracellular signal transduction pathways. Using the marine sponge Geodia cydonium we showed that during the initial phase of cell-cell contact the AF causes a rapid stimulation of the phosphatidylinositol pathway, resulting in an activation of protein kinase C and a subsequent phosphorylation of DNA topoisomerase II. As one consequence of these processes, the cells undergo a phase of high DNA synthesis. However, at later stages, the AF loses its mitogenic activity; this function is then taken over by the matrix lectin. During this switch, the lectin receptor associates in the plasma membrane with the ras oncogene product. The description of these processes is subject of this review article.

Animals↗

PubMed1998

Intercellular interactions as a basis for the expedient behaviour of multicellular systems.

Functional and structural aspects of intercellular interactions are considered. Chemical substances are universal mediators of intercellular interactions. Electrical and mechanical interactions are also involved in cell-cell cooperation. Functional peculiarities of the two principal types of intercellular interactions-ligand-receptor interactions and interactions based on permeable contacts-are compared. Examples of basic tissue processes are given (such as the mechanisms of embryonic induction and differentiation, regulation of cell proliferation, temporal and spatial regulation of the activity of differentiated cells, interactions between excitable cells) to illustrate the notion that the types of intercellular interactions are mutually complementary and fulfill different functions. Ligand-receptor interactions predominantly provide signal functions and ensure intertissue interactions, while the interactions based on permeable contacts mainly fulfill intratissue coordination relying on positional information and the exchange of energy and matter.

Cell Communication↗

PubMed2006

Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network.

In multicellular organisms, the ability to regulate reproduction, development, and nutrient utilization coincided with the evolution of nuclear receptors (NRs), transcription factors that utilize lipophilic ligands to mediate their function. Studying the expression profile of NRs offers a simple, powerful way to obtain highly relational information about their physiologic functions as individual proteins and as a superfamily. We surveyed the expression of all 49 mouse NR mRNAs in 39 tissues, representing diverse anatomical systems. The resulting data set uncovers several NR clades whose patterns of expression indicate their ability to coordinate the transcriptional programs necessary to affect distinct physiologic pathways. Remarkably, this regulatory network divides along the following two physiologic paradigms: (1) reproduction, development, and growth and (2) nutrient uptake, metabolism, and excretion. These data reveal a hierarchical transcriptional circuitry that extends beyond individual tissues to form a meganetwork governing physiology on an organismal scale.

Animals↗

PubMed2005

In my end is my beginning: control of end resection and DSBR pathway 'choice' by cyclin-dependent kinases.

The genome is constantly subjected to chemical alterations that have the potential to cause genetic mutation, chromosomal rearrangements and, in the case of multicellular organisms, cancer. Particular vulnerability exists during DNA replication, when the two DNA strands of a chromosome separate to form templates for the synthesis of sister chromatids. Attempted replication across a damaged or nicked DNA template can result in the formation of a double-strand break (DSB), arguably the most dangerous of DNA lesions. DSBs can also arise directly at any cell cycle stage following exposure to ionizing radiation or radiomimetic agents. To combat these recurrent threats of genomic instability, numerous distinct enzyme systems have evolved that sense DNA damage and coordinate its repair. Part of this coordination involves the activation of signal transduction cascades that target repair proteins, trigger DNA damage-dependent cell cycle checkpoints and profoundly affect chromatin neighboring a DSB. Here, we discuss current models of how lesion processing itself helps to coordinate these signals in dividing cells. Recent evidence in yeast of a role for cyclin-dependent kinases in DNA end resection suggests a possible solution to the long-standing puzzle of how DSBR pathway 'choice' is regulated through the cell cycle.

Cyclin-Dependent Kinases↗

PubMed1991

Mathematical modeling for the aging process: normal, abnormal and self-terminating phenomena in spatio-temporal organization.

An elucidation of the aging process is attempted using a simple one-dimensional multicellular system, a prototype of living organisms. This model analysis has the advantage of making us investigate the two types of modes of their dynamical behavior: (i) the local modes of behavior of individual cells and (ii) the global modes of behavior of the total system. At first, each cell is assumed to have biochemically excitable kinetics for local modes, and then what kind of the global modes results with change in intercellular interaction is examined. With a simple interaction as possibly occurs in the early stage of differentiation, the model displays well-coordinated spatio-temporal patterns. This may be interpreted as a normal state. With a more complex interaction as possibly occurs in the late stage of growth, however, the model produces much more erratic patterns. This may refer to an abnormal state. Interestingly, these abnormal patterns can be transformed into normal patterns, when the activity of some parts of this model is turned 'off'; the system can survive at the sacrifice of its parts. This makes us imagine that programmed cell death plays an important role in development during morphogenesis. When individual cells become less sensitive to intercellular signals and still possess intrinsic excitability, then the normal patterns are developed for a short while before being replaced by rather irregular patterns. As time proceeds, however, all activity of them disappears. We call this a 'self-terminating' phenomenon, which may refer to aging. This strongly suggests that the loss of the total system function, leading to death, results from a global mode of system failure but not from a local mode of subsystem failure.

Aging↗

PubMed1983

A network thermodynamic approach to the Hill-King and Altman approach to kinetics: computer simulation.

The network simulation of kinetic systems is a rather painless way to produce dynamic analogs of these models without becoming involved in needless mathematical difficulty. The methods of King and Altman, Hill, Mason, and others fall into a universal paradigm applicable in both the kinetic and thermodynamic coordinate systems. (It is a small extra step to turn the state concentrations into chemical potentials and affinities using diode subcircuits during any simulation. This will be spelled out in detail in future work. Thus the simulation can be carried out using the exact kinetic rate laws, but the results are readily put into a form which allows the energetics to be analyzed as well). Another virtue of network modeling and simulation is the hierarchical nature of the networks and its correspondence to that of the living system. It is now possible to simulate complicated multicellular epithelial membranes with channels and/or carriers in certain selected cell membranes. The only limitation to progress in this area is the lack of experimental information to feed into the models. On the other hand, the network models are rapidly becoming an indispensable aid in experimental design for precisely this reason. Living systems have always been characterized by their morphology to a great extent. There is no reason why that morphology can be ignored as their function is analyzed. In the past, it often had to be simplified due to the weakness of the analytical tools available. Now, by utilizing the same methods that have caused an explosion of progress in electronics, it is possible to hope to understand the structure-function relationship of living systems with equal facility. The challenge remaining is to develop experimental techniques which will keep up with the demand for information generated by the models.

Animals↗