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PubMedDate not supplied

Sequential steps of carbohydrate signaling mediate sensory afferent differentiation.

Differences in carbohydrate signaling control sequential steps in synaptic growth of sensory afferents in the leech. The relevant glycans are constitutive and developmentally regulated modifications of leechCAM and Tractin (family members of NCAM and L1) that are specific to the surface of sensory afferents. A mannosidic glycosylation mediates the dynamic growth of early afferents as they explore their target region through sprouting sensory arbors rich with synaptic vesicles. Later emerging galactosidic glycosylations serve as markers for subsets of the same sensory afferents that correlate with different sensory modalities. These developmentally regulated galactose markers now oppose the function of the constitutive mannose marker. Sensory afferents gain cell-cell contact with central neurons and self-similar afferents, but lose filopodia and synaptic vesicles. Extant vesicles are confined to sites of en passant synapse formation. The transformation of sensory afferent growth, progressing from mannose- to galactose-specific recognition, is consistent with a change from cell-matrix to cell-cell contact. While the constitutive mannosidic glycosylation promotes dynamic growth, developmentally regulated galactosidic glycosylations of the same cell adhesion molecules promote tissue stability. The persistence of both types of neutral glycans beyond embryonic age allows their function in synaptic plasticity during habituation and learning.

Afferent Pathways↗
PubMed2006

Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short-term facilitation and increase in short-term depression during postnatal development.

Schaffer collateral excitatory synapses onto CA1 pyramidal cells are subject to significant modulation by short-term plasticity. This presynaptic, history-dependent modulation of neurotransmitter release causes synaptic transmission to be sensitive to the frequency of the input. As a result, temporally irregular input patterns, such as those observed in vivo, produce synaptic responses over a very wide dynamic range that reflect a balance of short-term facilitation and short-term depression. The neonatal period is an important developmental period in the hippocampus, when functional representations of an animal's environment are being established through exploratory behavior. The strength of excitatory synapses and their modulation by short-term plasticity are critical to this process. One form of short-term plasticity, paired-pulse facilitation, has been shown to decrease as juvenile rats mature into young adults. However, little is known about the neonatal modulation of other forms of short-term plasticity, including the responses to temporally complex stimuli. We examined developmental modulation of the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 pyramidal cells in acute hippocampal slices, using both constant frequency stimuli and natural stimulus patterns that were taken from in vivo recording of spike patterns of hippocampal cells. In response to constant frequency stimulation, synapses in slices from young adult rats (P28-P35) showed less short-term depression than did those in slices from juveniles (P12-P18). However, when the natural stimulus pattern (containing a wide mix of frequencies) was used, synapses from young adults instead showed more short-term depression and less short-term facilitation than did juveniles. Comparing the natural stimulus pattern responses with constant frequency stimulation of a similar frequency, we found that the average responses were similar in young adults (both showed modest depression). However, in juveniles, the natural pattern produced robust facilitation while constant frequency stimulation caused a large short-term depression. Our results reveal that there are developmental changes both in individual forms of short-term plasticity and in the relative balance between short-term facilitation and short-term depression that will alter the signal transfer characteristics of these synapses.

Animals↗
PubMed2003

Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development.

T cells develop through distinct stages directed by a series of signals. We explored the roles of SWI/SNF-like BAF chromatin remodeling complexes in this process by progressive deletion of the ATPase subunit, Brg, through successive stages of early T cell development. Brg-deficient cells were blocked at each of the developmental transitions examined. Bcl-xL overexpression suppressed cell death without relieving the developmental blockades, leading to the accumulation of Brg-deleted cells that were unexpectedly cell cycle arrested. These defects resulted partly from the disruptions of pre-TCR and potentially Wnt signaling pathways controlling the expression of genes such as c-Kit and c-Myc critical for continued development. Our studies indicate that BAF complexes dynamically remodel chromatin to propel sequential developmental transitions in response to external signals.

Adenosine Triphosphatases↗
PubMed2005

The Drosophila dosage compensation complex binds to polytene chromosomes independently of developmental changes in transcription.

In Drosophila, the dosage compensation complex (DCC) mediates upregulation of transcription from the single male X chromosome. Despite coating the polytene male X, the DCC pattern looks discontinuous and probably reflects DCC dynamic associations with genes active at a given moment of development in a salivary gland. To test this hypothesis, we compared binding patterns of the DCC and of the elongating form of RNA polymerase II (PolIIo). We found that, unlike PolIIo, the DCC demonstrates a stable banded pattern throughout larval development and escapes binding to a subset of transcriptionally active areas, including developmental puffs. Moreover, these proteins are not completely colocalized at the electron microscopy level. These data combined imply that simple recognition of PolII machinery or of general features of active chromatin is either insufficient or not involved in DCC recruitment to its targets. We propose that DCC-mediated site-specific upregulation of transcription is not the fate of all active X-linked genes in males. Additionally, we found that DCC subunit MLE associates dynamically with developmental and heat-shock-induced puffs and, surprisingly, with those developing within DCC-devoid regions of the male X, thus resembling the PolIIo pattern. These data imply that, independently of other MSL proteins, the RNA-helicase MLE might participate in general transcriptional regulation or RNA processing.

Animals↗
PubMedDate not supplied

A conceptual model for care in developmental disability services.

The aim of this paper is to develop a personal conceptual framework with which to examine the nature of care for people with developmental disabilities in group homes. It examines the nature of care and its corollary self-care, both in general terms as well as those specific to the field of developmental disability. It also analyses the nature of nursing and its relationship to the care and training of people with developmental disabilities. From this, a conceptual framework is constructed based upon the dynamics of care which stem from the personal experience of developmental disability.

Group Homes↗
PubMed2005

Differentiation-dependent alterations in histone methylation and chromatin architecture at the inducible chicken lysozyme gene.

It is now well established that locus-wide chromatin remodeling and dynamic alterations of histone modifications are required for the developmentally regulated activation of tissue-specific genes. However, little is known about the dynamics of these events during cell differentiation and how chromatin of an entire gene locus responds to signal transduction processes. To address this issue we investigated chromatin accessibility, linker histone distribution, and the histone methylation status at the macrophage-specific chicken lysozyme locus and the ubiquitously expressed gas41 locus in multipotent precursor cell lines and BM2 monoblast cells. The latter can be induced to go through macrophage maturation by treatment with phorbol-12-myristate acetate and can be further stimulated with bacterial lipopolysaccharide. We show that expression of the lysozyme gene in undifferentiated monoblasts is low and that a high level of gene expression requires both cell differentiation and lipopolysaccharide stimulation. However, depletion of the linker histone H1 is observed already in lysozyme non-expressing multipotent precursor cells. In undifferentiated monoblasts, the lysozyme regulatory regions are marked by the presence of monomethylated histone H3 lysine 4, which becomes increasingly converted into trimethylated H3 lysine K4 during cell differentiation. We also present evidence for extensive, differentiation-dependent alterations in nuclease accessibility at the lysozyme promoter without alterations of nucleosome and transcription factor occupancy.

Animals↗
PubMed2003

Development as a dynamic system.

Development is about creating something more from something less, for example, a walking and talking toddler from a helpless infant. One current theoretical framework views the developmental process as a change within a complex dynamic system. Development is seen as the emergent product of many decentralized and local interactions that occur in real time. We examine how studying the multicausality of real-time processes could be the key to understanding change over developmental time. We specifically consider recent research and theory on perseverative reaching by infants as a case study that demonstrates this approach.

Journal Article↗
PubMed2002

Yan regulates Lozenge during Drosophila eye development.

The Drosophila eye offers an excellent opportunity to understand how general developmental processes are subtly altered to result in specific cell fates. Numerous transcription factors have been characterized in the developing eye; most of these are active in overlapping subsets of cells. Mechanisms used to regulate transcription factors act at many levels, and include competition for cognate binding sites, post translational modification, transcriptional regulation and cofactor availability. In undifferentiated cells of the larval eye imaginal disc, the transcriptional repressor Yan outcompetes the transcriptional activator Pointed for ETS binding sites on the prosperoenhancer. During differentiation, the Ras signaling cascade alters the Yan/Pointed dynamic through protein phosphorylation, effecting a developmental switch. In this way, Yan and Pointed are essential for prospero regulation. Hyperstable Yan (ACT) cannot be phosphorylated and blocks prospero expression. Lozenge is expressed in undifferentiated cells, and is required for prospero regulation. We sequenced the eye-specific enhancer of lozenge in three Drosophila species spanning 17 million years of evolution and found complete conservation of three ETS consensus binding sites. We show that lozengeexpression increases as cells differentiate, and that Yan (ACT) blocks this upregulation at the level of transcription. We find that expression of Lozenge via an alternate enhancer alters the temporal expression of Prospero, and is sufficient to rescue Prospero expression in the presence of Yan (ACT). These results suggest that Lozenge is involved in the Yan/Pointed dynamic in a Ras-dependent manner. We propose that upregulated Lozenge acts as a cofactor to alter Pointed affinity, by a mechanism that is recapitulated in mammalian development.

Animals↗
PubMed2000

Developmental expression of pim kinases suggests functions also outside of the hematopoietic system.

We have cloned a novel quail cDNA with strong homology to the pim family of proto-oncogenes. The deduced amino acid (aa) sequence of the cDNA, named qpim, is more closely related to Xenopus Pim and to the recently identified rat Pim-3 than to human or rodent Pim-1 or Pim-2. The protein encoded by the qpim cDNA can autophosphorylate itself and share substrates with murine Pim-1, suggesting functional redundancy to other Pim family serine/threonine kinases. We have compared the expression of qpim in avian embryos to mouse pim-1, -2 and -3 by in situ hybridization. qpim shows a highly dynamic expression pattern, particularly at early developmental stages. Surprisingly, its expression pattern is not identical to any of the murine pim genes, which show complementary and/or partially overlapping expression sites both in- and outside of the hematopoietic system. Altogether, our results suggest novel functions for Pim family kinases during embryonic development, in particular in epithelia and in the central nervous system.

Abdomen↗
PubMed1991

The dynamic structure of rabbit blastocyst coverings. III. Transformation of coverings under non-physiological developmental conditions.

Under physiological conditions the zona pellucida disappears in the rabbit between Day 3 and early Day 4 post coitum (p.c.) and is replaced by a new layer, the neozona. The dissolution of the zona pellucida and the formation of the neozona was investigated in three different experimental approaches, all of them characterized by non-physiological developmental conditions for the embryo: Prevention of embryo migration from the oviduct into the uterus by postcoital (48 h p.c.) tubal ligation, in vitro culture, and asynchronous embryo transfer into uteri of recipient rabbits. Embryos of age 2 1/2, 3, 4 and 4 1/2 days p.c. were cultured for 12 to 72 h. The media used for in vitro culture were supplemented with BSA, serum or with uterine secretions that were collected either synchronously or asynchronously to the developmental stage of the cultured embryos. Three-day-old embryos were transferred into uteri of pseudopregnant foster rabbits of either synchronous (Day 3) or asynchronous stages (Day 0, 2, 4, 5, 6) and were recovered 24 to 72 h after transfer. The transformation of the coverings was evaluated by light and transmission electron microscopy. The dissolution of the zona pellucida was greatly disturbed in tube-locked embryos, and in cultured embryos if standard protein supplements (BSA or serum) had been used for in vitro culture. In many cases the zona was still completely preserved after 2 or 3 days in culture, at a time when it normally would have already been replaced by the neozona in vivo. The dissolution in vitro, however, progressed incomparably better if the culture medium had been substituted with synchronous or asynchronous uterine secretions. The formation of the neozona could not be verified in cultured blastocysts. After embryo transfer, the dissolution of the zona pellucida was completed in most cases by 2 days after transfer, irrespective of the recipients' progestational stage. Present results indicate that uterine components are essential for the dissolution of the rabbit zona pellucida. These components appear to be present in the uterine cavity constitutively, i.e. independently of the uterine progestational transformation, and need not be in synchrony with the embryo's developmental stage for dissolution of the zona. Normal formation of the neozona does not take place under the non-physiological developmental conditions of in vitro culture.

Animals↗
PubMed2006

Myosin I and actin dynamics: the frogs weigh in.

In this issue of Developmental Cell, Sokac et al. (2006) describe an intriguing new role for an actin-based motor protein in restraining actin polymerization during endocytosis in Xenopus oocytes.

Actins↗
PubMed2004

Microtubular spindle dynamics and chromosome complements from somatic cell nuclei haploidization in mature mouse oocytes and developmental potential of the derived embryos.

BACKGROUND: The aim of this study was to investigate haploidization of somatic cell nuclei in non-enucleated mature oocytes regarding spindle formation, chromosomes and developmental potential. METHODS: Mouse cumulus cells were injected into metaphase II oocytes. Some injected oocytes were examined for morphological changes of chromosomes and the spindle immediately, and at 30 min, 1 h or 2 h after the injections. The remaining oocytes were activated by Sr(2+) after various incubation periods and observed for formation of a second polar body and pseudo-polar body. Cytogenetic analysis was performed for some of the resulting zygotes. The progress to blastocysts in vitro and the possibility of conception in vivo were assessed. RESULTS: Immediately after injection, the cumulus cell nucleus was still in interphase without spindle formation. The occurrence of premature chromosome condensation (PCC) and spindle formation increased as the incubation time increased. The percentages of activated oocytes increased with the incubation time after nuclear transfer, but the difference was not significant between 1 (58%) and 2 h (62%). The incidence of chromosomal aberrations was high for the derived embryos. Development in vitro was poor, and no procreation of pups occurred after transfer of the 324 embryos. CONCLUSIONS: The PCC and spindle formation induced by cumulus cell nuclei in mature oocytes was time dependent, as was the chance for successful activation. The chromosomal abnormalities from segregation errors presented one obvious cause, apart from the potential epigenetic defects, of developmental failure of the semi-cloned embryos.

Animals↗
PubMed2001

Metabotropic glutamate receptors mGluR1alpha and mGluR2/3 display dynamic expression patterns in developing rat striatum.

The developmental expression of two metabotropic glutamate receptors (mGluR), mGluR1alpha and mGluR2/3 was evaluated in the rat striatum from birth to adulthood. The mGluR1alpha receptor subtype displayed a patchy organization perinatally that became more homogeneous after the first postnatal week. The adult pattern of receptor expression consisted of homogeneous punctate profiles spread throughout the striatum. The mGluR2/3 receptor subtype exhibited a unique pattern of ontogenic expression, being associated exclusively with fibers of the internal capsule that penetrate the striatum, during the perinatal period. The protein localization for this subtype spread into the striatal neuropil after the first postnatal week, in parallel to the development of afferent terminations and arborizations to the nucleus. Unlike the ionotropic GluR subunits that are associated with somata and dendrites, neither subtype of metabotropic receptor was associated with neuronal cell bodies within the striatum.

Animals↗
PubMed2005

Cloning and developmental expression of Xenopus Enabled (Xena).

Regulation of actin dynamics, organization, and interaction with cell surface adhesion proteins is critical for tissue morphogenesis during development. The Ena/VASP family of actin-binding proteins function in several cellular processes that involve dynamic regulation of the actin cytoskeleton, including axon guidance, platelet aggregation, cell migration, and cell adhesion. The vertebrate Ena/VASP family is composed of three genes: Ena (Enabled), VASP (Vasodilator Stimulated Phosphoprotein), and Evl (Ena/VASP-Like). To better understand the role of Ena/VASP proteins during vertebrate development, we have cloned and characterized the developmental expression of Ena in Xenopus laevis. Analysis of the temporal expression of Xenopus Ena (Xena) demonstrates that multiple isoforms of Xena are detected throughout embryogenesis and that the presence of different isoforms is developmentally regulated. In situ hybridization analyses reveal that Xena is broadly expressed throughout development. During gastrulation and neurulation, Xena is detected in the neuroepithelium, notochord, and somites. In tadpoles, Xena expression is restricted to dorsal regions of the brain, whereas it is expressed at lower levels throughout the spinal cord. Xena expression is also detected in the notochord, myotome, heart, pronephros, and cranial placodes, including the olfactory and otic placodes. Analysis of the subcellular localization of Xena using a GFP fusion protein revealed that Xena localizes to adherens junctions and focal adhesions in Xenopus animal caps and NIH3T3 fibroblasts, respectively. These results define spatiotemporal windows in which Xena may function during early Xenopus development to modulate actin-dependent processes such as cell adhesion and migration.

Amino Acid Sequence↗
PubMed1999

The constructivist brain.

How do the representations underlying cognitive skills emerge? It is becoming increasingly apparent that answering this question requires integration of neural, cognitive and computational perspectives. Results from this integrative approach resonate with Piaget's central constructivist themes, thus converging on a 'neural constructivist' approach to development, which itself rests on two major research developments. First, accumulating neural evidence for developmental plasticity makes nativist proposals increasingly untenable. Instead, the evidence suggests that cortical development involves the progressive elaboration of neural circuits in which experience-dependent neural growth mechanisms act alongside intrinsic developmental processes to construct the representations underlying mature skills. Second, new research involving constructivist neural networks is elucidating the dynamic interaction between environmentally derived neural activity and developmental mechanisms. Recent neurodevelopmental studies further accord with Piaget's themes, supporting the view of human cortical development as a protracted period of hierarchical-representation construction. Combining constructive growth algorithms with the hierarchical construction of cortical regions suggests that cortical development involves a cascade of increasingly complex representations. Thus, protracted cortical development, while occurring at the expense of increased vulnerability and parental investment, appears to be a powerful and flexible strategy for constructing the representations underlying cognition.

Journal Article↗
PubMed2006

Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD).

Amyloidogenic processing of the amyloid precursor protein (APP) results in the generation of beta-amyloid, the main constituent of Alzheimer plaques, and the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential; however, the targets of AICD-dependent gene regulation and hence the physiological role of AICD remain largely unknown. We analyzed transcriptome changes during AICD-dependent gene regulation by using a human neural cell culture system inducible for expression of AICD, its coactivator FE65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton, including alpha2-Actin and Transgelin (SM22). AICD target genes were also found to be differentially regulated in the frontal cortex of Alzheimer's disease patients compared with controls as well as in AICD/FE65 transiently transfected murine cortical neurons. Confocal image analysis of neural cells and cortical neurons expressing both AICD and FE65 confirmed pronounced changes in the organization of the actin cytoskeleton, including the destabilization of actin fibers and clumping of actin at the sites of cellular outgrowth. Our data point to a role of AICD in developmental and injury-related cytoskeletal dynamics in the nervous system.

Actins↗
PubMed2004

Variability in /s/ production in children and adults: evidence from dynamic measures of spectral mean.

Previous research has found developmental decreases in temporal variability in speech. Relatively less work has examined spectral variability, and, in particular, variability in consonant spectra. This article examined variability in productions of the consonant /s/ by adults and by 3 groups of children, with mean ages of 3;11 (years;months), 5;04, and 8;04. Specifically, it measured the influence of age, phonetic context, and syllabic context on variability. Spectral variability was estimated by measuring dynamic spectral characteristics of multiple productions of /s/ in sV, spV, and swV sequences, where the vowel was either /a/ or /u/. Mean duration, variability in duration, and coarticulation were also measured. Children were found to produce /s/ with greater temporal and spectral variability than adults. Duration and coarticulation were comparable across the 4 age groups. Spectral variability was greater in swV contexts than in sV or spV sequences. The lack of consistent effects of phonetic context on spectral variability suggests that the developmental differences were related to subtle variability in place of articulation for /s/ in the children's productions.

Adult↗