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PubMed2002

Genetic "code": representations and dynamical models of genetic components and networks.

Dynamical modeling of biological systems is becoming increasingly widespread as people attempt to grasp biological phenomena in their full complexity and make sense of an accelerating stream of experimental data. We review a number of recent modeling studies that focus on systems specifically involving gene expression and regulation. These systems include bacterial metabolic operons and phase-variable piliation, bacteriophages T7 and lambda, and interacting networks of eukaryotic developmental genes. A wide range of conceptual and mathematical representations of genetic components and phenomena appears in these works. We discuss these representations in depth and give an overview of the tools currently available for creating and exploring dynamical models. We argue that for modeling to realize its full potential as a mainstream biological research technique the tools must become more general and flexible, and formal, standardized representations of biological knowledge and data must be developed.

Animals↗
PubMed2003

Oogenesis in Drosophila melanogaster: a model system for studying cell differentiation and development.

Drosophila oogenesis is a complex developmental process involving the coordinated differentiation of germ line and somatic cells. Correct execution and timing of cell fate specification and patterning events is achieved during this process by the integration of different cell-cell signalling pathways, eventually leading to the generation of positional information inside the oocyte, that is instrumental for the establishment of embryonic polarity. The large body of data accumulated at both cellular and molecular levels in the last decade clearly demonstrated how Drosophila oogenesis is a genetically tractable system particularly suited for the investigation of key developmental biology questions. Our recent contribution to the field relies on the characterisation of three different mutants named tegamino (teg), hold hup (hup) and tulipano (tip), identifying novel gene functions required during oogenesis. Specifically, teg is implicated in the morphogenesis of the follicular epithelium surrounding the germ line cells in the egg chamber, hup is involved in the establishment of egg chamber polarity and tip in the regulation of the dynamic germ cell chromatin organisation.

Animals↗
PubMedDate not supplied

Infants' attention to patterned stimuli: developmental change from 3 to 12 months of age.

To examine the development of look duration as a function of age and stimulus type, 14- to 52-week-old infants were shown static and dynamic versions of faces, Sesame Street material, and achromatic patterns for 20 s of accumulated looking. Heart rate was recorded during looking and parsed into stimulus orienting, sustained attention, and attention termination phases. Infants' peak look durations indicated that prior to 26 weeks there was a linear decrease with age for all stimuli. Older infants' look durations continued to decline for patterns but increased for Sesame Street and faces. Measures of heart rate change during sustained attention and the proportion of time spent in each phase of attention confirmed infants' greater engagement with the more complex stimuli.

Arousal↗
PubMed1985

The cellular dynamics of pattern formation in the eye of Drosophila.

The establishment and early development of the ommatidial bundles in the presumptive eye of Drosophila have been investigated using electron microscopic serial sectioning. A progression of developmental stages has been characterized. Initially simple, symmetrically constructed bundles develop into asymmetrical, more complex constructions. Computer graphic reconstruction has been used to show the three-dimensional structure of the various ommatidial bundles. Autoradiography has been used to locate the position of a region of cell division which is intimately associated with the formation of the ommatidial bundles.

Animals↗
PubMed2005

Developmental regulation of Suz 12 localization.

Chromatin modifications are among the epigenetic alterations essential for genetic reprogramming during development. The Polycomb group (PcG) gene family mediates chromatin modifications that contribute to developmentally regulated transcriptional silencing. Trimethylation of histone H3 on lysine 27, mediated by a PcG protein complex consisting of Eed, Ezh2, and Suz12, is integral in differentiation, stem cell self-renewal, and tumorigenesis. Eed and Ezh2 are also implicated in the developmentally regulated silencing of the inactive X chromosome, as they are transiently enriched on the inactive X chromosome when X chromosome silencing is initiated. Here we analyze the dynamic localization of Suz12 during cellular differentiation and X-inactivation. Though Suz12 is a requisite member of the Eed/Ezh2 complexes, we found that Suz12 exhibits a notable difference from Ezh2 and Eed: while Ezh2 and Eed levels decrease during stem cell differentiation, Suz12 levels remain constant. Despite the differential regulation in abundance of Suz12 and Eed/Ezh2, Suz12 is also transiently enriched on the Xi during early stages of X-inactivation, and this accumulation is Xist RNA dependent. These results suggest that Suz12 may have a function that is not mediated by its association with Eed and Ezh2, and that this additional function is not involved in the regulation of X-inactivation.

Animals↗
PubMed1993

Practical applications from chaos theory to the psychotherapeutic process, a basic consideration of dynamics.

This essay contains speculations about the import of some ideas from chaos theory for psychotherapeutic process. Brief consideration is given to areas of psychology in which such ideas have been applied, as well as some ideas on psychic energy. Then, using a psychodynamic perspective as a base, three aspects of psychotherapy are addressed, the container, the process, and the clinician as the agent of change. A central idea is that the emotional experience of chaos is a necessary developmental step. It is important for the therapist to recognize whether a client is avoiding this experience or is overwhelmed by this experience.

Anxiety↗
PubMed2002

Secreted Frizzled-related proteins: searching for relationships and patterns.

Secreted Frizzled-related proteins (SFRPs) are modulators of the intermeshing pathways in which signals are transduced by Wnt ligands through Frizzled (Fz) membrane receptors. The Wnt networks influence biological processes ranging from developmental cell fate, cell polarity and adhesion to tumorigenesis and apoptosis. In the five or six years since their discovery, the SFRPs have emerged as dynamically expressed proteins able to bind both Wnts and Fz, with distinctive structural properties in which cysteine-rich domains from Fz- and from netrin-like proteins are juxtaposed. The abundant expression of SFRP genes in the early embryo, altered expression patterns in disease states, and potential significance in the evolution of the vertebrate body plan, make these intriguing molecules relevant to investigations in diverse fields of biology and biomedical sciences.

Animals↗
PubMed2005

Transcriptional co-regulation of secondary metabolism enzymes in Arabidopsis: functional and evolutionary implications.

The combined knowledge of the Arabidopsis genome and transcriptome now allows to get an integrated view of the dynamics and evolution of metabolic pathways in plants. We used publicly available sets of microarray data obtained in a wide range of different stress and developmental conditions to investigate the co-expression of genes encoding enzymes of secondary metabolism pathways, in particular indoles, phenylpropanoids, and flavonoids. We performed hierarchical clustering of gene expression profiles and found that major enzymes of each pathway display a clear and robust co-expression throughout all the conditions studied. Moreover, detailed analysis evidenced that some genes display co-regulation in particular physiological conditions only, certainly reflecting their modular recruitment into stress- or developmentally regulated biosynthetic pathways. The combination of these microarray data with sequence analysis allows to draw very precise hypotheses on the function of otherwise uncharacterized genes. To illustrate this approach, we focused our analysis on secondary metabolism glycosyltransferases (UGTs), a multigenic family involved in the conjugation of small molecules to sugars like glucose. We propose that UGT74B1 and UGT74C1 may be involved in aromatic and aliphatic glucosinolates synthesis, respectively. We also suggest that UGT75C1 may function as an anthocyanin-5-O-glucosyltransferase in planta. Therefore, this data-mining approach appears very powerful for the functional prediction of unknown genes, and could be transposed to virtually any other gene family. Finally, we suggest that analysis of expression pattern divergence of duplicated genes also provides some insight into the mechanisms of metabolic pathway evolution.

Arabidopsis↗
PubMed1981

Prepubertal ontogeny of responsiveness to estradiol in female rat central nervous system.

The physiological response to systemic estrogens changes dramatically during the period from birth to puberty. With the onset of puberty, the rat reaches a critical developmental plateau with regard to endocrinological responsiveness to estradiol. Since the appearance of the pubertal response pattern appears to be less a consequence of some intrinsic "trigger' than the natural continuation of a developmental sequence that begins prenatally, its ontogeny should be examined in a broad context that will take account of the impact of each of the dynamic components influencing the interactions between estradiol and the central nervous system on the functional development of the organism as a whole. The prepubertal ontogeny of endocrinological responsiveness to estradiol in the central nervous system of the female rat is examined in the context of several of the important factors that are known to influence the functional development of the hypothalamo-pituitary-gonadal circuit:the rapidly changing hormonal environment of the morphologically and physiologically immature juvenile rat, the shifting predominance of alphafetoprotein and "adult" estradiol-binding protein, sexual differentiation of the neural substrate, and the development of mature pituitary-gonadal feedback mechanisms. The availability of ever more sensitive techniques for the measurement of the actions of estradiol in the central nervous system of the immature organism has necessitated a re-evaluation of existing data. This, in turn, suggests that new approaches should be applied to the examination of problems related to the development of reproductive maturity of the central nervous system.

Animals↗
PubMed1990

Neurotransmitters and neuromodulators in the basal ganglia.

The basal ganglia have become a focus for work on neurotransmitter interactions in the brain. These structures contain a remarkable diversity of neuroactive substances, organized into functional subsystems that have unique developmental histories and vulnerabilities in neurodegenerative diseases. A new view of the basal ganglia is emerging on the basis of this neurochemical heterogeneity, suggesting that dynamic regulation of transmitter expression may be a key to extrapyramidal function.

Animals↗
PubMed2006

Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine.

The target of rapamycin (TOR) signaling pathway regulates cell growth and proliferation, however the extent to which TOR signaling mediates particular organogenesis programs remains to be determined. Here we report an examination of TOR signaling during zebrafish development, using a combination of small molecule treatment and morpholino-mediated gene knockdown. First, we amplified and sequenced the full-length cDNA for the zebrafish TOR ortholog (ztor). By in situ hybridization, we found that ztor is expressed ubiquitously in the early embryo, but displays a dynamic pattern in the gut between 48 and 72 h post-fertilization (hpf). Treatment of zebrafish embryos with rapamycin induced only a mild general developmental delay up to 72 hpf, but digestive tract development became arrested at the primitive gut tube stage. Rapamycin inhibited intestinal epithelial growth, morphogenesis and differentiation. Using morpholino-mediated gene knockdown of TOR pathway components, we show that this effect is mediated specifically by the rapamycin-sensitive TOR complex 1 (TORC1). Thus, in addition to regulating cell growth and proliferation, TOR signaling controls the developmental program guiding epithelial morphogenesis in the vertebrate intestine.

Animals↗
PubMed1994

[Physiology, psychology and pathology of writing and spelling--an overview].

Writing and spelling are conceived as concerted actions comprising cognitive planning, motor action and an expressive content. In literate societies the individual use of alphabetic systems is acquired immediately after speech as a "cultural technique". As such these systems demand specific cognitive and motor skills which have been analysed primarily on the basis of neurological and psychiatric syndromes. We distinguish primary developmental disturbances and secondarily acquired disturbances of writing and spelling, categorizing the latter into four essential disturbance areas: linguistic command, motor execution, automatism control and dynamic tonus regulation. The clinical significance of writing and spelling is not confined to its possible disturbances. In pathologically induced restrictions of cognitive functions or of social skills the fact is rather that the written language frequently contributes to the development of individual coping strategies. From the psychodynamic aspect, written communication is characterized principally by its proximity-regulating function.

Handwriting↗
PubMed2004

A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation.

The nuclear receptor corepressor (NCoR) and the related factor known as silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) are essential components of multiprotein complexes that mediate active repression by unliganded nuclear receptors. Recent studies suggest that NCoR and SMRT can interact with and exert repressive effects on several other classes of DNA-binding transcription factors, but the physiological importance of these interactions has not been established. Here, investigation of endogenous transcriptional programs regulated by NCoR in macrophages reveals that NCoR acts as a transcriptional checkpoint for activator protein (AP)-1-dependent gene networks that regulate diverse biological processes including inflammation, cell migration, and collagen catabolism, with loss of NCoR, resulting in derepression of AP-1 target genes. The NCoR corepressor complex imposes an active block of exchange of c-Jun for c-Jun/c-Fos heterodimers, with targeted deletion of the c-Jun locus, resulting in loss of NCoR complexes from AP-1 target genes under basal conditions. The checkpoint function of NCoR is relieved by signal-dependent phosphorylation of c-Jun, which directs removal of NCoR/HDAC3/TBL1/TBLR1 complexes through recruitment of a specific ubiquitylation complex, as a prerequisite to the default binding of c-Jun/c-Fos heterodimers and transcriptional activation. The requirement for a checkpoint function to achieve the appropriate dynamic range of transcriptional responses to inflammatory signals is likely to be used by other signal-dependent transcription factors that regulate diverse homeostatic and developmental processes.

Animals↗
PubMed2005

Strategies to maintain redox homeostasis during photosynthesis under changing conditions.

Plants perform photosynthesis and assimilatory processes in a continuously changing environment. Energy production in the various cell compartments and energy consumption in endergonic processes have to be well adjusted to the varying conditions. In addition, dissipatory pathways are required to avoid any detrimental effects caused by over-reduction. A large number of short-term and long-term mechanisms interact with each other in a flexible way, depending on intensity and the type of impact. Therefore, all levels of regulation are involved, starting from energy absorption and electron flow events through to post-transcriptional control. The simultaneous presence of strong oxidants and strong reductants during oxygenic photosynthesis is the basis for regulation. However, redox-dependent control also interacts with other signal transduction pathways in order to adapt metabolic processes and redox-control to the developmental state. Examples are given here for short-term and long-term control following changes of light intensity and photoperiod, focusing on the dynamic nature of the plant regulatory systems. An integrating network of all these mechanisms exists at all levels of control. Cellular homeostasis will be maintained as long as the mechanisms for acclimation are present in sufficiently high capacities. If an impact is too rapid, and acclimation on the level of gene expression cannot occur, cellular damage and cell death are initiated.

Adaptation, Physiological↗
PubMed2003

Competitive fates of bacterial social parasites: persistence and self-induced extinction of Myxococcus xanthus cheaters.

Cooperative biological systems are susceptible to disruption by cheating. Using the social bacterium Myxococcus xanthus, we have tested the short-term competitive fates of mixed cheater and wild-type strains over multiple cycles of cooperative development. Cheater/wild-type mixes underwent several cycles of starvation-induced multicellular development followed by spore germination and vegetative population growth. The population sizes of cheater and wild-type strains in each pairwise mixture were measured at the end of each developmental phase and each growth phase. Cheater genotypes showed several distinct competitive fates, including cheater persistence at high frequencies with little effect on total population dynamics, cheater persistence after major disruption of total population dynamics, self-extinction of cheaters with wild-type survival, and total population extinction. Our results empirically demonstrate that social exploitation can destabilize a cooperative biological system and increase the risk of local extinction events.

Biological Evolution↗
PubMed2016

Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.

Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution.

Animals↗
PubMed2003

Temporal and spatial regulation in prokaryotic cell cycle progression and development.

Bacteria exhibit a high degree of intracellular organization, both in the timing of essential processes and in the placement of the chromosome, the division site, and individual structural and regulatory proteins. We examine the temporal and spatial regulation of the Caulobacter cell cycle, bacterial chromosome segregation and cytokinesis, and Bacillus subtilis sporulation. Mechanisms that control timing of cell cycle and developmental events include transcriptional cascades, regulated phosphorylation and proteolysis of signal transduction proteins, transient genetic asymmetry, and intercellular communication. Surprisingly, many signal transduction proteins are dynamically localized to specific subcellular addresses during the cell division cycle and sporulation, and proper localization is essential for their function. The Min proteins that govern division site selection in Escherichia coli may be the first example of a system that generates positional information de novo.

Bacillus subtilis↗
PubMed1996

Follistatins and alpha 2-macroglobulin are soluble binding proteins for inhibin and activin.

Inhibin is a 32-kD dimeric glycoprotein consisting of an alpha subunit and one of two beta subunits (beta A or beta B), which was isolated and cloned on the basis of its ability to inhibit FSH release from the pituitary. Activin results from the combination of two inhibins. Activins can cause stimulation of FSH release from pituitary cells both in vitro and in vivo, and in addition are involved in embryogenesis, erythropoiesis, and reproductive function. The inhibin-related peptides, and their receptors, are present in the testis and ovary from early gestation through adulthood. An additional level of control of the activity of growth factors is afforded by specific binding which may regulate protein turnover, localization and bioactivity. To date, two distinct binding proteins for inhibin and activin have been identified, both of which are expressed in the testes and other tissues and are present in the circulation. In serum, inhibin is primarily found associated with alpha 2-macroglobulin (alpha 2M), a high-capacity, low-affinity binding protein which binds many cytokines and growth factors. Binding to alpha 2M does not appear to alter immuno- or bioactivity of inhibin or activin. The second binding protein, follistatin, is produced in many of the same tissues which produce the activin and inhibin. This molecule may function primarily as a regulator of activin bioavailability and bioactivity. The affinity of follistatin for activin (< 0.1 nM) is similar to that of the high-affinity activin receptors. Thus, dynamic changes in the relative levels of the amount of any of these components could act to modulate activin and inhibin bioavailability in both a developmentally and tissue-restricted pattern in the testes and ovary.

Activins↗