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Core binding factor in the early avian embryo: cloning of Cbfbeta and combinatorial expression patterns with Runx1.

We have isolated the avian ortholog for CBFbeta, the common non-DNA binding subunit of the core binding factor (CBF) that has important regulatory roles in major developmental pathways. CBFbeta forms heterodimers with the DNA-binding Runx proteins and increases their affinity for DNA and their protein stability. Here, we describe the Cbfbeta expression pattern during the first 4 days of chick embryo development, with a special interest in the developing hematopoietic system. We have compared its expression pattern to that of Runx1, which is crucial for the generation of definitive hematopoietic cells, and to other hematopoietic- or endothelial-specific markers (c-Myb, Pu.1, CD45, c-Ets-1 and VE-Cadherin). Initially, Cbfbeta is widely expressed in the early mesoderm in both the yolk sac and the embryo proper, but later its expression becomes restricted to specific organs or cell types. We have found that Cbfbeta expression overlaps with Runx1 in the hematopoietic system and neural tube. The somitic and mesonephric structures, however, express Cbfbeta in the absence of detectable Runx1. Finally, Cbfbeta and Runx1 display multiple combinatorial patterns in the endoderm and in specific nerves or ganglia. Taken together, we show that Cbfbeta exhibits a dynamic expression pattern that varies according to the organ, cell type or developmental stage. By revealing multiple combinatorial patterns between Cbfbeta and Runx1, these data provide new insights into the role of CBF during early development.

Amino Acid Sequence↗

Computer-mediated interdisciplinary teams: theory and reality.

The benefit of experience, tempered with the wisdom of hindsight and 5 years of text-based, asynchronous, computer-mediated, interdisciplinary team communications, provides the energy, insights and data shared in this article. Through the theoretical lens of group dynamics and the epistemology of interdisciplinary teaming, we analyze the interactions of a virtual interdisciplinary team to provide an understanding and appreciation of collaborative interdisciplinary communication in the context of interactive technologies. Whilst interactive technologies may require new patterns of language similar to that of learning a foreign language, what is communicated in the interdisciplinary team process does not change. Most important is the recognition that virtual teams, similar to their face-to-face counterparts, undergo the same challenges of interdisciplinary teaming and group developmental processes of formation: forming, storming, norming, performing, and transforming. After examining these dynamics of communication and collaboration in the context of the virtual team, the article concludes with guidelines facilitating interdisciplinary team computer-mediated communication.

Computer-Assisted Instruction↗

2-D and 3-D computed tomography and magnetic resonance imaging in developmental dysplasia of the hip.

Clinical examination and plain roentgenograms have been the main methods of diagnosis and treatment of developmental dysplasia of the hip. Occasionally, concentric reduction cannot be achieved, or the reduction is questionable. A dynamic arthrogram can add more information but is usually performed under general anesthesia. "Mini" computed tomographic imaging demonstrates the femoral head-acetabulum relationship more accurately and produces minimal radiation. Three-dimensional computed tomography is useful in older children, in whom all sections are ossified. Magnetic resonance imaging, particularly 3-D magnetic resonance imaging, demonstrates the nonossified structures. It is the best method of visualization in developmental dysplasia of the hip. The disadvantages of this method include its cost and the lack of dynamic imaging. In the future, new software will overcome these shortcomings.

Acetabulum↗

The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling.

The integrin family of cell adhesion receptors are important for a diverse set of biological responses during development. Although many integrins have been shown to engage a similar set of cytoplasmic effector proteins in vitro, the importance of these proteins in the biological events mediated by different integrin receptors and ligands is uncertain. We have examined the role of one of the best-characterized integrin effectors, the focal adhesion protein paxillin, by disruption of the paxillin gene in mice. Paxillin was found to be critically involved in regulating the development of mesodermally derived structures such as heart and somites. The phenotype of the paxillin(-/-) mice closely resembles that of fibronectin(-/-) mice, suggesting that paxillin is a critical transducer of signals from fibronectin receptors during early development. Paxillin was also found to play a critical role in fibronectin receptor biology ex vivo since cultured paxillin-null fibroblasts display abnormal focal adhesions, reduced cell migration, inefficient localization of focal adhesion kinase (FAK), and reduced fibronectin-induced phosphorylation of FAK, Cas, and mitogen-activated protein kinase. In addition, we found that paxillin-null fibroblasts show some defects in the cortical cytoskeleton and cell spreading on fibronectin, raising the possibility that paxillin could play a role in structures distinct from focal adhesions. Thus, paxillin and fibronectin regulate some common embryonic developmental events, possibly due to paxillin modulation of fibronectin-regulated focal adhesion dynamics and organization of the membrane cytoskeletal structures that regulate cell migration and spreading.

Animals↗

Bone microstructure and developmental plasticity in birds and other dinosaurs.

Patterns of bone microstructure have frequently been used to deduce dynamics and processes of growth in extant and fossil tetrapods. Often, the various types of primary bone tissue have been associated with different bone deposition rates and more recently such deductions have extended to patterns observed in dinosaur bone microstructure. These previous studies are challenged by the findings of the current research, which integrates an experimental neontological approach and a paleontological comparison. We use tetracycline labeling and morphometry to study the variability of bone deposition rates in Japanese quail (Coturnix japonica) growing under different experimental conditions. We compare resulting patterns in bone microstructure with those found in fossil birds and other dinosaurs. We found that a single type of primary bone varies significantly in rates of growth in response to environmental conditions. Ranging between 10-50 microm per day, rates of growth overlap with the full range of bone deposition rates that were previously associated with different patterns of bone histology. Bone formation rate was significantly affected by environmental/experimental conditions, skeletal element, and age. In the quail, the experimental conditions did not result in formation of lines of arrested growth (LAGs). Because of the observed variation of bone deposition rates in response to variation in environmental conditions, we conclude that bone deposition rates measured in extant birds cannot simply be extrapolated to their fossil relatives. Additionally, we observe the variable incidence of LAGs and annuli among several dinosaur species, including fossil birds, extant sauropsids, as well as nonmammalian synapsids, and some extant mammals. This suggests that the ancestral condition of the response of bone to environmental conditions was variable. We propose that such developmental plasticity in modern birds may be reduced in association with the shortened developmental time during the later evolution of the ornithurine birds.

Animals↗

Trouble ahead: predicting antisocial trajectories with dynamic systems concepts and methods.

This paper reviews and evaluates a set of studies that utilize dynamic systems (DS) principles, and in two cases dynamic systems methods, for predicting antisocial development and other behavioral outcomes. I suggest that the emphasis of DS approaches on process and nonlinear causation is very different from the emphasis in developmental psychopathology on prediction, yet the marriage of these approaches is necessary to capture the complex interactions that give rise to problematic trajectories. The studies reviewed do indeed uncover predictive relations that would have been difficult to conceptualize or impossible to find using more traditional strategies. In discussing these studies. I suggest DS interpretations of emerging individual differences, phase-specific change, sleeper effects, mediating variables, and behavioral rigidity versus malleability, in the context of developmental prediction. I also discuss the advantages of moving from DS concepts to DS methods in clinical-developmental research.

Conduct Disorder↗

A Global Workspace perspective on mental disorders.

BACKGROUND: Recent developments in Global Workspace theory suggest that human consciousness can suffer interpenetrating dysfunctions of mutual and reciprocal interaction with embedding environments which will have early onset and often insidious staged developmental progression, possibly according to a cancer model, in which a set of long-evolved control strategies progressively fails. METHODS AND RESULTS: A rate distortion argument implies that, if an external information source carries a damaging 'message', then sufficient exposure to it, particularly during critical developmental periods, is sure to write a sufficiently accurate image of it on mind and body in a punctuated manner so as to initiate or promote similarly progressively punctuated developmental disorder, in essence either a staged failure affecting large-scale brain connectivity, which is the sine qua non of human consciousness, or else damaging the ability of embedding goal contexts to contain conscious dynamics. CONCLUSION: The key intervention, at the population level, is clearly to limit exposure to factors triggering developmental disorders, a question of proper environmental sanitation, in a large sense, primarily a matter of social justice which has long been known to be determined almost entirely by the interactions of cultural trajectory, group power relations, and economic structure, with public policy. Intervention at the individual level appears limited to triggering or extending periods of remission, representing reestablishment of an extensive, but largely unexplored, spectrum of evolved control strategies, in contrast with the far better-understood case of cancer.

Brain↗

Hematopoietic stem cells and aging.

The question of whether hematopoietic stem cells are altered in aging has been the subject of considerable controversy for over two decades. The substantial advancement of knowledge on hematopoietic stem cells and developmental hematology in the last few years has reopened this issue for critical analysis. Dynamic changes have been noted regarding the anatomic site and the function of hematopoietic cells, from the early embryo to old age. Whereas basal hematopoietic potential is maintained in aging. the capacity for recovery from hematological stress and for stem cell self-renewal appears to decline gradually. A distinction is thus made between the steady-state hematopoiesis in aging and the developmental potential of stem cells. The establishment of proper tools to identify and to study purified stem cells and committed cell populations offers a direct approach to further elucidate aging across the axis from primitive stem cells to the mature blood cells. The present article represents a brief review of this area.

Aging↗

Quantitative assessment of tumor oxygen dynamics: molecular imaging for prognostic radiology.

One of the fundamental molecules governing the survival of mammalian cells is oxygen. Oxygen has gained particular significance in tumor developmental biology and oncology. An increasingly diverse array of methods is now available to characterize tumor oxygenation. This Prospect will consider a new method, Fluorocarbon Relaxometry using Echo planar imaging for Dynamic Oxygen Mapping (FREDOM), which we have recently developed for oximetry, examine application to a specific therapeutic example and place this technique in the context of other approaches.

Administration, Inhalation↗

A dynamic model for the morphogenesis of the late vertebrate lens.

A mathematical model is presented for the morphogenesis of the post-vesicular vertebrate lens with an umbilical suture. The lens is modeled as having four compartments: anterior epithelium (germinative and central anterior zones), recruitment zone (transitional zone), cortex (discrete concentric cohorts of secondary cortex fiber cells, each cohort treated individually), and nucleus. Equations are written to describe the time evolution of the cohorts; their shapes collectively determine the shape of the lens. The growth of cell volume is exponential, with different rates in the cortex and epithelium; recruitment of epithelium cells into the cortex is described as resulting from an overproduction of epithelial basal (capsular) surface in the anterior epithelium. The equations contain three dimensionless numbers determined by the physiology of the epithelium and cortex cells. Solutions are stable attractors in a morphological space. All solutions entail exponential growth of the lens diameter; a portion of parameter space corresponds to exponential growth superimposed on large amplitude oscillations in lens shape. Emergent time-scales for increase in lens size and oscillation period are an order of magnitude longer than the cellular growth time-scales. The lens shapes tend to a family of stable scaling solutions, the shapes of which remain unchanged as the lens grows. The model is applied to morphological data for the chick and lamprey lenses. The dynamics described are seen as exemplifying an auto-regulatory morphogenesis process wherein a system passes through a sequence of developmental stages. Each stage is characterized by its own fixed informing geometry (a set of defining spatial relationships), within which a growth process unfolds autonomously, generating a dynamically stable structure. The developing system invokes a means of forgetting dated structural information; this dissipation is necessary to the pattern formation process.

Animals↗

A joint model for nonparametric functional mapping of longitudinal trajectory and time-to-event.

BACKGROUND: The characterization of the relationship between a longitudinal response process and a time-to-event has been a pressing challenge in biostatistical research. This has emerged as an important issue in genetic studies when one attempts to detect the common genes or quantitative trait loci (QTL) that govern both a longitudinal trajectory and developmental event. RESULTS: We present a joint statistical model for functional mapping of dynamic traits in which the event times and longitudinal traits are taken to depend on a common set of genetic mechanisms. By fitting the Legendre polynomial of orthogonal properties for the time-dependent mean vector, our model does not rely on any curve, which is different from earlier parametric models of functional mapping. This newly developed nonparametric model is demonstrated and validated by an example for a forest tree in which stemwood growth and the time to first flower are jointly modelled. CONCLUSION: Our model allows for the detection of specific QTL that govern both longitudinal traits and developmental processes through either pleiotropic effects or close linkage, or both. This model will have great implications for integrating longitudinal and event data to gain better insights into comprehensive biology and biomedicine.

Algorithms↗

Reorganization in coping behavior at 1 1/2 years: dynamic systems and normative change.

By the age of 1 year toddlers demonstrate distinct coping habits for dealing with frustration. However, these habits may be open to change and reorganization at subsequent developmental junctures. We investigated change in coping habits at 18-20 months, a normative age for major advances in social cognition, focusing on the dynamic systems principles of fluctuation and novelty at transitions. Specifically, we asked whether month-to-month fluctuation, novel behavioral habits and real-time variability increased at the age of a normative transition, despite individual differences in the content of behavior. Infants were given frustrating toys while their mothers sat nearby without helping, on monthly visits at 14-25 months (before, during and after the hypothesized transition). State space grids representing patterns of behavioral durations were constructed for each episode and compared over age. As predicted, month-to-month fluctuation in grid patterns increased temporarily between 17 and 20 months, partly independently of a concurrent peak in distress, and new behavioral habits replaced old ones at the same age. Coping habits changed differently for high-and low-distressed toddlers. However, changes in real-time variability did not generally meet our expectations.

Adaptation, Psychological↗

Developmental science, systems of care, and prevention of emotional and behavioral problems in youth.

Developmental science, a metatheoretical framework for investigating individual development across the lifecourse, is discussed in terms of its application to prevention and treatment of emotional and behavioral problems. The multifaceted, dynamic, and bidirectional contribution of factors, both internal and external to the individual, is thus emphasized. Key aspects of developmental science, systems of care, and prevention are described, and the implications for delivery of mental health services to children and youth are discussed.

Adolescent↗

Expression dynamics of WOX genes mark cell fate decisions during early embryonic patterning in Arabidopsis thaliana.

During embryonic pattern formation, the main body axes are established and cells of different developmental fates are specified from a single-cell zygote. Despite the fundamental importance of this process, in plants, the underlying mechanisms are largely unknown. We show that expression dynamics of novel WOX (WUSCHEL related homeobox) gene family members reveal early embryonic patterning events in Arabidopsis. WOX2 and WOX8 are co-expressed in the egg cell and zygote and become confined to the apical and basal daughter cells of the zygote, respectively, by its asymmetric division. WOX2 not only marks apical descendants of the zygote, but is also functionally required for their correct development, suggesting that the asymmetric division of the plant zygote separates determinants of apical and basal cell fates. WOX9 expression is initiated in the basal daughter cell of the zygote and subsequently shifts into the descendants of the apical daughter apparently in response to signaling from the embryo proper. Expression of WOX5 shows that identity of the quiescent center is initiated very early in the hypophyseal cell, and highlights molecular and developmental similarities between the stem cell niches of root and shoot meristems. Together, our data suggest that during plant embryogenesis region-specific transcription programs are initiated very early in single precursor cells and that WOX genes play an important role in this process.

Amino Acid Sequence↗

Rapid high resolution three dimensional reconstruction of embryos with episcopic fluorescence image capture.

One of the overarching goals in developmental biology is the elucidation of mechanisms that elaborate form and function. To this end, an accurate morphological description of embryonic development is essential. However, visualizing dynamic changes in the three-dimensional (3D) structure of the developing embryo has been a "holy grail" in the field of developmental biology. The fundamental difficulties that have hindered all efforts in 3D reconstruction using two-dimensional (2D) image stacks revolve around the seemingly intractable problems of section registration and distortion. A remarkably simple solution has come about with the development of a new technique referred to as episcopic fluorescence image capture (EFIC). With EFIC imaging, tissue autofluorescence is used to image the block face prior to cutting each section. The 2D resolution obtained is close to that achieved by histology, and such 2D image stacks can be readily reconstructed in 3D. The 3D models generated provide fine structural details with resolution unmatched by 3D reconstructions obtained with any other imaging modalities. Given the perfect registration of EFIC image stacks, another important capability provided by EFIC is digital resectioning in any plane. This provides complete flexibility in the selection of optimal virtual sectioning planes for viewing different features in a specimen, and is invaluable for analyzing dynamic changes in tissue structure in the developing embryo. The capabilities provided by EFIC for rapid high resolution 3D reconstruction together with digital resectioning make this an unparalleled tool for characterizing morphogenetic events in the developing embryo. Although our review is focused on using EFIC for studying embryonic development, it is important to note that there is no intrinsic limitation on the size of the specimen that can be analyzed by EFIC imaging. Overall, EFIC should serve as an important imaging technique that will complement other 3D imaging modalities such as MRI and optical tomography. Given the feasibility of generating EFIC image stacks using cryoembedded or polyethylene glycol (PEG)-embedded specimens, there is the possibility that EFIC may be combined with 3D RNA or protein expression profiling. Together, such studies may help further elucidate the relationship between form and function.

Animals↗

Developmental decrease in synaptic facilitation at the mouse hippocampal mossy fibre synapse.

Transmission at the hippocampal mossy fibre (MF)-CA3 pyramidal cell synapse is characterized by prominent activity-dependent facilitation, which is thought to provide a wide dynamic range in hippocampal informational flow. At this synapse in mice the magnitude of paired-pulse facilitation and frequency-dependent facilitation markedly decreased with postnatal development from 3 weeks (3W) to 9 weeks (9W). Throughout this period the mean amplitude and variance of unitary EPSCs stayed constant. By altering extracellular Ca2+/Mg2+ concentrations the paired-pulse ratio could be changed to a similar extent as observed during development. However, this was accompanied by an over 30-fold change in EPSC amplitude, suggesting that the developmental change in facilitation ratio cannot simply be explained by a change in release probability. With paired-pulse stimulation the Ca2+ transients at MF terminals, monitored using mag-fura-5, showed a small facilitation, but its magnitude remained similar between 3W and 9W mice. Pharmacological tests using CNQX, adenosine, LY341495, H-7 or KN-62 suggested that neither presynaptic receptors (kainate, adenosine and metabotropic glutamate) nor protein kinases are responsible for the developmental change in facilitation. Nevertheless, loading the membrane-permeable form of BAPTA attenuated the paired-pulse facilitation in 3W mice to a much greater extent than in 9W mice, resulting in a marked reduction in age difference. These results suggest that the developmental decrease in the MF synaptic facilitation arises from a change associated with residual Ca2+, a decrease in residual Ca2+ itself or a change in Ca2+-binding sites involved in the facilitation. A developmental decline in facilitation ratio reduces the dynamic range of MF transmission, possibly contributing to the stabilization of hippocampal circuitry.

Aging↗

Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development.

The lung develops from the endoderm through a process of branching morphogenesis. This process is highly active during the pseudoglandular stage of lung development and continues into the canalicular stage, resulting in the formation of terminal sacs. CCAAT/enhancer binding proteins (C/EBPs) are transcription factors regulating central aspects of differentiation and proliferation. We report here the developmental expression of C/EBPalpha, -beta, and -delta in the lung. C/EBPalpha exhibits a dynamic expression pattern and is first detected during the late pseudoglandular stage. At this stage, expression is observed in a subset of epithelial cells in the distal parts of the branching tubules. The expression of C/EBPalpha is confined to nonproliferating cells. To examine the role of C/EBPalpha in lung development, we generated transgenic mice ectopically expressing C/EBPalpha in the lung epithelium using the human surfactant protein C promoter. Lungs from these mice were of normal size but exhibited a phenotype characterized by fewer and larger developing epithelial tubules, indicating that the branching process was affected. No effects on overall proliferation or cellular differentiation were observed. When this phenotype was compared with that of mice carrying a targeted mutation of the Cebpa gene, the Cebpa-/- mice exhibited a similar developmental phenotype. In conclusion, our results show a role for C/EBPalpha in lung development and suggest a function in the later stages of lung branching morphogenesis.

Animals↗

Dynamic regulation of BDNF and NT-3 expression during visual system development.

Recent studies have proposed roles for neurotrophins in the formation and plasticity of ocular dominance columns as well as in the regulation of dendritic arborization in visual cortex of higher mammals. To assess potential roles for neurotrophins in these processes, we have examined the developmental expression of BDNF and NT-3 mRNA in the cat's visual system using in situ hybridization. BDNF and NT-3 mRNAs are dynamically regulated in many CNS structures during embryonic and postnatal development, and both mRNAs undergo striking developmental changes in laminar specificity and levels of expression within primary visual cortex during the critical period for ocular dominance column formation. Within visual cortex, BDNF mRNA is found in neurons in deep cortical layers (5 and 6) prior to eye opening, and in both deep and superficial layers (2 and 3) shortly afterwards. Within layer 4, the target of thalamocortical axons, BDNF mRNA is low initially and rises to high levels by the end of the critical period for ocular dominance column formation. NT-3 mRNA is first detectable in small stellate neurons at the base of layer 4 (4c) after eye opening, and levels decrease near the end of the critical period. BDNF and NT-3 mRNAs can be detected in the lateral geniculate nucleus at birth, and levels peak during the critical period. In both structures, BDNF mRNA expression is maintained into adulthood, while NT-3 is undetectable in the adult. The presence and dynamic regulation of these neurotrophins in visual structures is consistent with suggested roles for both of these neurotrophins in axonal and dendritic remodeling known to accompany the formation of ocular dominance columns.

Age Factors↗