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Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology.

The dynamic changes in dendritic morphology displayed by developing and mature neurons have stimulated interest in deciphering the signaling pathways involved. Recent studies have identified megakaryocytic acute leukemia (MAL), a serum response factor (SRF) co-activator, as a key component of a signaling pathway linking changes in the actin cytoskeleton to SRF-mediated transcription. To help define the role of this pathway in regulating dendritic morphology, we have characterized the pattern of MAL expression in the developing and adult brain, and have examined its role in regulating dendritic morphology in cultured cortical neurons. In histological studies of mouse brain, we found prominent expression of MAL in neurons in adult hippocampus and cerebral cortex. MAL immunostaining revealed localization of this protein in neuronal cell bodies and apical dendrites. During development, an increase in MAL expression occurs during the second post-natal week. Expression of dominant negative MAL constructs or MAL siRNA in cortical neurons grown in primary culture reduces the number of dendritic processes and decreases the basal level of SRF-mediated transcription. Taken together, these findings indicate that the MAL-SRF signaling pathway plays a key role in regulating dendritic morphology.

Animals↗

Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development.

RBM is a germ-cell-specific RNA-binding protein encoded by the Y chromosome in all mammals, implying an important and evolutionarily conserved (but as yet unidentified) function during male germ cell development. In order to address this function, we have developed new antibody reagents to immunolocalise RBM in the different cell types in the human testis. We find that RBM has a different expression profile from its closest homologue hnRNPG. Despite its ubiquitous expression in all transcriptionally active germ cell types, RBM has a complex and dynamic cell biology in human germ cells. The ratio of RBM distributed between punctate nuclear structures and the remainder of the nucleoplasm is dynamically modulated over the course of germ cell development. Moreover, pre-mRNA splicing components are targeted to the same punctate nuclear regions as RBM during the early stages of germ cell development but late in meiosis this spatial association breaks down. After meiosis, pre-mRNA splicing components are differentially targeted to a specific region of the nucleus. While pre-mRNA splicing components undergo profound spatial reorganisations during spermatogenesis, neither heterogeneous ribonucleoproteins nor the transcription factor Sp1 show either developmental spatial reorganisations or any specific co-localisation with RBM. These results suggest dynamic and possibly multiple functions for RBM in germ cell development.

Cyclic AMP Response Element Modulator↗

Ringing in the new ear: resolution of cell interactions in otic development.

The vertebrate inner ear is a marvel of structural and functional complexity, which is all the more remarkable because it develops from such a simple structure, the otic placode. Analysis of inner ear development has long been a fascination of experimental embryologists, who sought to understand cellular mechanisms of otic placode induction. More recently, however, molecular and genetic approaches have made the inner ear a useful model system for studying a much broader range of basic developmental mechanisms, including cell fate specification and differentiation, axial patterning, epithelial morphogenesis, cytoskeletal dynamics, stem cell biology, neurobiology, physiology, etc. Of course, there has also been tremendous progress in understanding the functions and processes peculiar to the inner ear. The goal of this review is to recount how historical approaches have shaped our understanding of the signaling interactions controlling early otic development; to discuss how new findings have led to fundamental new insights; and to point out new problems that need to be resolved in future research.

Animals↗

Functional mapping - how to map and study the genetic architecture of dynamic complex traits.

The development of any organism is a complex dynamic process that is controlled by a network of genes as well as by environmental factors. Traditional mapping approaches for analysing phenotypic data measured at a single time point are too simple to reveal the genetic control of developmental processes. A general statistical mapping framework, called functional mapping, has been proposed to characterize, in a single step, the quantitative trait loci (QTLs) or nucleotides (QTNs) that underlie a complex dynamic trait. Functional mapping estimates mathematical parameters that describe the developmental mechanisms of trait formation and expression for each QTL or QTN. The approach provides a useful quantitative and testable framework for assessing the interplay between gene actions or interactions and developmental changes.

Animals↗

Emergence of pattern in the development of mammalian movement sequences.

The manner in which behavior is patterned in space and over time represents a fundamental problem in both ethology and neuroscience. Prior to the analysis of mechanism it is important to be sensitive to issues involved in the provision of descriptive taxonomies. Often alternative modes of description lead to different perspectives and research strategies. In both the development of behavioral patterns and their expression a major question is how underlying organizational systems become self-organizing through the process of mutual interactions. It is clear that simple static dichotomies in both behavioral and developmental science must be replaced by more sophisticated models that emphasize the dynamics of pattern formation and control. Some of these perspectives are illustrated from our ongoing research on rodent movement patterns.

Animals↗

Plasmodesmata: composition, structure and trafficking.

Plasmodesmata are highly specialized gatable trans-wall channels that interconnect contiguous cells and function in direct cytoplasm-to-cytoplasm intercellular transport. Computer-enhanced digital imaging analysis of electron micrographs of plasmodesmata has provided new information on plasmodesmatal fine structure. It is now becoming clear that plasmodesmata are dynamic quasi-organelles whose conductivity can be regulated by environmental and developmental signals. New findings suggest that signalling mechanisms exist which allow the plasmodesmatal pore to dilate to allow macromolecular transport. Plant viruses spread from cell to cell via plasmodesmata. Two distinct movement mechanisms have been elucidated. One movement mechanism involves the movement of the complete virus particle along virus-induced tubular structures within a modified plasmodesma. Apparently two virus-coded movement proteins are involved. A second movement mechanism involves the movement of a non-virion form through existing plasmodesmata. In this mechanism, the viral movement protein causes a rapid dilation of existing plasmodesmata to facilitate protein and nucleic acid movement. Techniques for the isolation of plasmodesmata have been developed and information on plasmodesma-associated proteins is now becoming available. New evidence is reviewed which suggests that plasmodesmatal composition and regulation may differ in different cells and tissues.

Biological Transport↗

Juvenile ageism: unrecognized prejudice and discrimination against the young.

Ageism is a form of prejudice and discrimination as virulent as racism and as pervasive as sexism. It has been described as it affects the elderly but has not been sufficiently recognized as it affects the young. Institutional juvenile ageism exists when social systems ignore the interests of children. Individual juvenile ageism exists when the developmental interests of a child are not respected. This article describes the dynamics, manifestations, and approaches to the amelioration of juvenile ageism.

Aged↗

The establishment, maintenance and productivity of a laboratory colony of Phlebotomus similis Perfiliew, 1963 (Diptera, Psychodidae).

Phlebotomus similis is a relatively poorly understood sand fly species. This paper presents the results of the first successful laboratory colonization of P. similis. Some bionomic factors collected on the life history, behaviour, feeding preferences, and characteristics of developmental biology of this species are described. Furthermore, the parameters of the dynamics and the life history of this species under laboratory conditions were quantified. These results will facilitate further studies necessary for understanding its potential role as a vector of leishmaniasis in the Mediterranean.

Animals↗

Extracellular matrix organized in embryonic cavities during induction of the embryonic axis in chick embryo.

Extracellular matrix (ECM) is detected as short, disorganized fibrils in the forming embryonic extracellular spaces shortly prior to the first morphogenetic cellular movements and interactions in the early chick embryo. As development progresses, the ECM is organized into an intricate network spanning the embryonic cavities. This dynamic entity undergoes relatively rapid changes in its organization pattern during the developmental period from morula to the induction of the neural plate. The ECM seems to preserve the exquisite architecture of the embryo and could guide migrating cells into defined pathways in the early embryo.

Animals↗

Sculpting heart valves with NFATc and VEGF.

Heart valves are of vital importance for our moment-to-moment existence, but how they form remains a mystery. In this issue of Cell, Chang et al. reveal a novel role for calcineurin, NFATs, and VEGF in valve formation. Dynamic changes in NFAT/VEGF expression in regional myocardial and endocardial fields and developmental windows orchestrate this complex process.

Animals↗

Repeatability of surface EMG during gait in children.

Although mean amplitude and ON-OFF timing of muscle recruitment and electromyography (EMG) activation during gait is achieved by an age of six to eight years in normally developing children, recruitment dynamics illustrated by the shape of the EMG waveform may require continued developmental practice to achieve a stable pattern. Previous analyses have quantified the repeatability of the EMG waveform in adult subjects, but EMG variability for a pediatric population may be significantly different. The goal of this study was to quantify intra-session and inter-session variability in the phasic EMG waveform patterns from the lower limb muscles during self-selected speeds of walking in healthy-normal children for comparison with adult variability in gait EMG. The variance ratio quantifies the repeatability of the integrated EMG waveform shape in a group of normally-developing children. Results reveal that between-session EMG waveform variability were similar in adult and pediatric populations, but within-session variability for the children was approximately twice the published value for adults. Clinical implications of this pediatric EMG variability suggest cautious interpretation of data from limited trial samples or inter-session changes in performance of gait data.

Analysis of Variance↗

Ca(2+)-independent spine dynamics in cultured hippocampal neurons.

Developing spines are highly dynamic processes that undergo rapid morphologic changes. We have investigated whether basal developmentally regulated spine motility is triggered by spontaneous changes in intracellular Ca(2+) ([Ca(2+)](i)). To address the link between Ca(2+) transients and motility, we have used the cell-permeable chelator BAPTA-AM. Consistent with others, we found that young cultured hippocampal neurons [7-13 days in vitro (DIV)] display significantly more spine motility than older neurons (14-21 days in vitro). Control experiments indicate that BAPTA-AM can lower basal [Ca(2+)](i) as well as block synaptically mediated Ca(2+) transients. However, globally buffering [Ca(2+)](i) by BAPTA-AM treatment failed to significantly alter the basal motility of developing spines measured at either relatively slow (5 min) or faster sampling times (every 20 s). We conclude that the basal spine motility of cultured hippocampal neurons may represent an intrinsic feature of developing neurons and is not necessarily choreographed by ongoing changes in [Ca(2+)](i) levels.

Aniline Compounds↗

Growth polarity and cell division in Streptomyces.

Streptomycetes are mycelial bacteria that resemble filamentous fungi in their apical growth, branching, and morphogenetic development. One inroad into the largely unknown mechanisms underlying this prokaryotic growth polarity is provided by Streptomyces DivIVA, a protein localized at hyphal tips and involved in tip extension. Another aspect is a proposed migration of nucleoids. During sporulation, the modes of growth and cell division are reorganised. This involves dynamic assembly of FtsZ into a multitude of cytokinetic rings. Controlled by developmental regulators and intriguingly coordinated with chromosome segregation, this leads to spores with a single chromosome each. Genome sequences have shed new light on these aspects and reinforced the role of Streptomyces in bacterial cell biology.

Chromosomes, Bacterial↗

Modeling the adaptive visual system: a survey of principled approaches.

Modeling the visual system can be done at multiple levels of description ranging from computer simulations of detailed biophysical models to firing rate and so-called 'black-box' models. Re-introducing David Marr's analysis levels for the visual system, we motivate the use of more abstract models in order to answer the question of what the visual system is computing. The approaches we selected to review in this article concentrate on modeling the changes of sensory representations. The considered time-scales, range from the developmental time-scale of receptive field formation to fast transient neuronal dynamics during a single stimulus presentation. Common to all approaches is their focus on providing functional interpretations, instead of 'only' explanations in terms of mechanisms. Although the concrete approaches can be distinguished along different lines, a common theme is emerging which may qualify as a paradigm for providing functional interpretations for changes of receptive field properties, i.e. the dynamic adjustment of sensory representations to varying external or internal conditions.

Adaptation, Physiological↗

Conditions of perceptual selection and suppression during interocular rivalry in strabismic and normal cats.

Presenting the two eyes with incongruent stimuli leads to the phenomenon of interocular rivalry. At any given time, one of the stimuli is perceptually suppressed in order to avoid double vision. In squinting subjects, rivalry occurs permanently also for congruent stimuli because of developmental rearrangement of cortical circuitry. In this study, we have investigated the dynamics and stimulus dependence of rivalry in six esotropic, four exotropic and three non-strabismic cats. As an indicator for perception, we used optokinetic nystagmus that was induced by moving gratings. The esotropic cats were tested for their visual acuity by means of a jumping stand procedure. The results show that one eye can dominate perception even if both eyes have equal visual acuity and are presented with stimuli of equal contrast. Strong eye dominance asymmetry was found in all but one of the tested cats. Notably, all three of the normal cats showed a clear asymmetry in perceptual selection. Measurements with varying contrast and velocity of the stimuli revealed that the influence of these parameters on perceptual selection was independent of the presence of strabismus. In all cats, the time during which a given eye dominated perception increased with the contrast and decreases with the velocity of the stimulus presented to this eye.

Animals↗

Formins: intermediates in signal-transduction cascades that affect cytoskeletal reorganization.

The control of cell growth and polarity depends on a dynamic actin cytoskeleton that has the ability to reorganize in response to developmental and environmental stimuli. In animals and fungi, formins are just one of the four major classes of poly-L-proline-containing (PLP) proteins that form part of the signal-transduction cascade that leads to rearrangement of the actin cytoskeleton. Analysis of the Arabidopsis genome sequence indicates that, unlike animals and fungi, formins are the only class of conserved profilin-binding PLP proteins in plants. Moreover, plant formins show significant structural differences compared with their animal and fungal counterparts, raising the possibility that plant formins are subject to novel mechanisms of control or perform unique roles in plants.

Actins↗

Sequential memory: a developmental perspective on its relation to frontal lobe functioning.

The multidimensional nature of the frontal lobes serves to organize and coordinate brain functionings playing a central and pervasive role in human cognition. The executive processes implicated in complex cognition such as novel problem solving, modifying behavior as appropriate in response to changes in the environment, inhibiting prepotent or previous responses, and the implementation of schemas that organize behavior over time are believed to be mediated by the frontal regions of the brain. Overall, the functioning of the frontal lobes assists individuals in goal directed and self-regulatory behavior. Additional theories of frontal lobe functioning have focused on its involvement in temporal, or time-related domains. The organizational and strategic nature of frontal lobe functioning affects memory processes by enhancing the organization of to-be-remembered information. Among the specific memory systems presumed to be based on anterior cerebral structures is the temporal organization of memory. An essential component of memory that involves temporal organization is sequential ordering entailing the ability to judge which stimuli were seen most recently and the temporal ordering of events in memory. Focal lesion studies have demonstrated the importance of the frontal lobes on retrieval tasks in which monitoring, verification, and placement of information in temporal and spatial contexts of critical importance. Similarly, frontal lobe damage has been associated with deficits in memory for the temporal ordering, or sequencing, of events. The acquisition of abilities thought to be mediated by the frontal lobes, including sequential memory, unfolds throughout childhood, serving to condition patterns of behavior for the rest of the brain. Development of the frontal regions of the brain is known to continue through late adolescence and into early adulthood, in contrast to the earlier maturation of other cortical regions. The developmental patterns of the frontal lobes are thought to involve a hierarchical, dynamic, and multistage process.

Child↗

Organization of leg movements in preterm infants.

This study describes and establishes baseline data of early movement in preterm infants using a sensitive and quantitative measurement system, kinematic analysis. Subjects were 10 infants born at 34 to 36 weeks gestational age. Spontaneous leg movements were videotaped, and a 10-second segment was digitized to provide kinematic data. The same infants were tested at 3 days and again at 40 weeks postgestational age. Data obtained were compared to evaluate changes with age. Results showed that all infants had organized movement as determined by high interjoint correlations and small phase lags. Movement durations were restricted at 550 and 765 msec for flexion and extension, respectively. Amplitude, velocity, pause durations, and joint angles differed among infants. Infant leg movements are highly organized synergies not disrupted by postnatal events. Differences in movements are attributed to dynamic interaction of elements in the motor control system in real and developmental time. Similar studies on high-risk or sick preterm infants may provide clues to early detection of neuromuscular dysfunction.

Biomechanical Phenomena↗