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PubMed2026

CD109 exhibits a dynamic expression pattern in coronary endothelium and endocardial-derived valve mesenchyme during heart development with preserved morphogenesis following endothelial-specific deletion.

BACKGROUND: CD109 encodes a GPI-linked glycoprotein that acts as a signaling modulator in the TGF-β pathway. CD109 has emerged in several genome-wide association studies as linked to coronary artery disease, myocardial infarction, and angina pectoris. Heterozygous loss-of-function mutations in CD109 have also been reported in patients with congenital heart defects, suggesting potential developmental relevance, though CD109 has never been investigated in the context of cardiovascular development. We previously identified Cd109 upregulation in murine atrioventricular valves undergoing myxomatous degeneration following a reduction of epicardial-derived cells. Here, we characterize Cd109 expression in the murine cardiovascular system and assess its function during development using in vitro and in vivo approaches. RESULTS: We found that Cd109 is strongly expressed in the endothelium of the coronary vasculature and in endocardial-derived subpopulations in the atrioventricular valves. This expression persists through key stages in cardiovascular development. Western blotting and immunostaining confirm endothelial expression in heart and lung tissues. siRNA-mediated knockdown of CD109 in primary human endothelial cells led to dysregulation of vascular development pathways and decreased tube formation capacity. We generated endothelial-specific Cd109 knockout mice, eliminating Cd109 expression from heart and lung tissues without overt consequences for atrioventricular valve or coronary vascular morphogenesis during heart development. CONCLUSION: CD109 exhibits a highly dynamic spatiotemporal expression pattern during cardiovascular development, with enriched expression in coronary endothelial cells and endocardial-derived subpopulations in the valves. Despite this striking developmental expression pattern, previously reported human genetic associations with cardiovascular diseases, and endothelial-associated phenotypes following siRNA-mediated CD109 knockdown in a primary human endothelial cell line, endothelial/endocardial-lineage deletion of Cd109 did not produce overt abnormalities in atrioventricular valve or coronary vascular morphogenesis during embryonic development. Collectively, these findings identify CD109 as a useful marker of coronary endothelial and endocardial-derived valve cell populations and suggest that CD109 may function in a context-dependent or modulatory manner rather than as an essential regulator of cardiovascular morphogenesis under normal developmental conditions.

CD109↗
PubMed2001

Dynamic analysis of inter-words time intervals: a method to analyze the structure of communicative signals.

Speech analyses are usually focused on words as signifiers ignoring inter-words time intervals (IWIs), which are related to the 'form' of speech, rather than to its 'content'. Applying the method of power spectrum analysis to inter-vocalizations time intervals of bird singing, underlying periodic processes were detected. In contrast, human IWIs revealed non-periodicity, which may be random or chaotic. To differentiate between these two possibilities, the non-linear dynamic methods of unstable periodic orbits and correlation dimension were applied to show that IWIs are characterized by a low dimensional chaotic attractor. Its correlation dimension of 3.2 +/- 1.1 suggests a minimum number of four variables underlying the system. The methods developed in the present communication can be further applied: (a) for the measurement of specific alterations in the processes underlying the form of speech in human disorders, i.e., schizophrenia, (b) for the assessment of normal and pathological developmental aspects of speech processes in children; (c) for comparing communicative signals between humans and other species.

Adult↗
PubMed2005

Developmental regulation of the beta-globin gene locus.

The beta-globin genes have become a classical model for studying regulation of gene expression. Wide-ranging studies have revealed multiple levels of epigenetic regulation that coordinately ensure a highly specialised, tissue- and stage-specific gene transcription pattern. Key players include cis-acting elements involved in establishing and maintaining specific chromatin conformations and histone modification patterns, elements engaged in the transcription process through long-range regulatory interactions, transacting general and tissue-specific factors. On a larger scale, molecular events occurring at the locus level take place in the context of a highly dynamic nucleus as part of the cellular epigenetic programme.

Animals↗
PubMed2006

Semaphorins and their receptors in lamprey CNS: Cloning, phylogenetic analysis, and developmental changes during metamorphosis.

The large, conserved semaphorin gene family encodes axon guidance molecules in both invertebrates and vertebrates. The primitive vertebrate lamprey diverged near the time of vertebrate origins and is useful for understanding the gene duplication events that led to the increased complexity of the vertebrate genome. We characterized the sequence and expression pattern of semaphorins and their receptors genes in the sea lamprey, Petromyzon marinus. We uncovered two members of the semaphorin family in sea lamprey. The first encodes a diffusible class 3 type semaphorin protein that is most similar to the human and mouse Sema3F (71% amino acid identity). The second encodes a transmembrane class 4 type semaphorin that is most similar to mouse Sema4D and human Sema4G, with 38% amino acid identity within the Sema domain. We also identified in lamprey two members of the semaphorin receptor family, lamprey Plexin A1 and Plexin A2. Phylogenetic analysis indicates that lamprey Sema3 and Sema4 represent precursor genes existing prior to the origin of the vertebrate Sema3A-G and Sema4A-G subfamilies. Therefore, the gene duplication event that gave rise to those subfamilies must have occurred after the divergence of jawed vertebrates from jawless fish. These semaphorins and plexins are expressed in unique and dynamic patterns in lamprey spinal cord and brain during development.

Animals↗
PubMed2001

Activation of rabbit oocytes: the impact of the Ca2+ signal regime on development.

Postfertilization manipulation of mammalian embryos results in various developmental alterations. To determine whether the manipulation of the Ca2+ regime causing oocyte activation is a valuable experimental means in helping understand the biological process by which embryos integrate signals from outside and later regulate gene expression, we linked Ca2+ signal parameters i.e. amplitude, number and frequency, with the efficiency and quality of postimplantation development. Freshly ovulated rabbit oocytes were subjected to repetitive and modulated Ca2+ influx. The results provide three major pieces of information. Firstly, the Ca2+ stimulus is the most efficient signal activating mammalian eggs when it is applied in a repetitive manner, the amplitude being the crucial factor. Secondly, the dynamics of early cleavage does not appear to be determined by either the frequency or the amplitude of modulation of the Ca2+ signal that activates the oocyte. Thirdly, amplitude and temporal modulation of the Ca2+ signal in the early minutes influences the developmental performance and the morphology of the rabbit parthenogenetic conceptus at day 11.5 of pregnancy. The results demonstrate the importance of epigenetic events during postfertilization as well as the possible uses of Ca2+ modulation in studying long term developmental effects.

Animals↗
PubMed2003

Tropomyosin isoforms from the gamma gene differing at the C-terminus are spatially and developmentally regulated in the brain.

Tropomyosin is an actin-binding protein responsible for stabilizing the actin microfilament system in the cytoskeleton of nonmuscle cells and is involved in processes such as growth, differentiation, and polarity of neuronal cells. From the gamma gene, at least 11 different isoforms have been described, with three different C-terminal exons used (9a, 9c, 9d). The precise roles that the different isoforms play are unknown. To examine the localization and hence determine the function of these isoforms in developing mouse, specific antibodies to exons 9a and 9c were made. These were used with previously developed 9d and N-terminal 1b antibodies on Western blots and immunohistochemical analysis of mouse brains. We were able to show that all three C-termini are used in the brain. 9c isoforms are highly enriched in brain and neural cells, and we also detected significant amounts of 9a-containing isoforms in brain. gamma gene activity is relatively constant in the brain, but the choice of C-terminus is developmentally regulated. A more detailed study of the brain revealed regional expression differences. The hippocampus, cerebellum, and cortex were analyzed in depth and revealed that different isoforms could be sorted into different neuronal compartments, which change with development for 9d. Furthermore, a comparison with a homologous exon to 9c from the alpha-tropomyosin gene showed that expression from these exons is related to the maturational state of the neuron, even though both are sorted differently intracellularly. These data suggest that the large numbers of tropomyosin isoforms are likely to have specific roles in microfilament dynamics and neural cell function.

Animals↗
PubMed2005

Single-minded, Dmef2, Pointed, and Su(H) act on identified regulatory sequences of the roughest gene in Drosophila melanogaster.

Roughest (Rst) is a cell adhesion molecule of the immunoglobulin superfamily that has multiple and diverse functions during the development of Drosophila melanogaster. The pleiotropic action of Rst is reflected by its complex and dynamic expression during the development of Drosophila. By an enhancer detection screen, we previously identified several cis-regulatory modules that mediate specific expression of the roughest gene in Drosophila developmental processes. To identify trans-regulators of rst expression, we used the Gal4/UAS system to screen for factors that were sufficient to activate Rst expression when ectopically expressed. By this method we identified the transcription factors Single-minded, Pointed.P1, and Su(H)-VP16. Furthermore, we showed that these factors and, in addition, Dmef2 are able to ectopically activate rst expression via the previously described rst cis-regulatory modules. This fact and the use of mutant analysis allocates the action of the transcription factors to specific developmental contexts. In the case of Sim, we could show that it regulates rst expression in the embryonic midline, but not in the optic lobes. Mutagenesis of Sim consensus binding sites in the regulatory module required for rst expression in the embryonic midline, abolished rst expression; indicating that the regulation of rst by Sim is direct.

Animals↗
PubMed2004

Galectins in teleost fish: Zebrafish (Danio rerio) as a model species to address their biological roles in development and innate immunity.

Cell surface glycans, such as glycocoproteins and glycolipids, encode information that modulates interactions between cells, or between cells and the extracellular matrix, by specifically regulating the binding to cell surface-associated or soluble carbohydrate-binding receptors, such as lectins. Rapid modifications of exposed carbohydrate moieties by glycosidases and glycosyltransferases, and the equally dynamic patterns of expression of their receptors during early development, suggest that both play important roles during embryogenesis. Among a variety of biological roles, galectins have been proposed to mediate developmental processes, such as embryo implantation and myogenesis. However, the high functional "redundancy" of the galectin repertoire in mammals has hindered the rigorous characterization of their specific roles by gene knockout approaches in murine models. In recent years, the use of teleost fish as alternative models for addressing developmental questions in mammals has expanded dramatically, and we propose their use for the elucidation of biological roles of galectins in embryogenesis and innate immunity. All three major galectin types, proto, chimera, and tandem-repeat, are present in teleost fish, and phylogenetic topologies confirm the expected clustering with their mammalian orthologues. As a model organism, the zebrafish (Danio rerio) may help to overcome limitations imposed by the murine models because it offers substantial advantages: external fertilization, transparent embryos that develop rapidly in vitro, a diverse toolbox of established methods to manipulate early gene expression, a growing collection of mutations that affect early embryonic development, availability of cell lines, and most importantly, an apparently less diversified galectin repertoire.

Amino Acid Sequence↗
PubMed2005

Molecular mechanisms of flower development: an armchair guide.

An afternoon stroll through an English garden reveals the breathtaking beauty and enormous diversity of flowering plants. The extreme variation of flower morphologies, combined with the relative simplicity of floral structures and the wealth of floral mutants available, has made the flower an excellent model for studying developmental cell-fate specification, morphogenesis and tissue patterning. Recent molecular genetic studies have begun to reveal the transcriptional regulatory cascades that control early patterning events during flower formation, the dynamics of the gene-regulatory interactions, and the complex combinatorial mechanisms that create a distinct final floral architecture and form.

Cell Differentiation↗
PubMed2026

BDNF-DT and BDNF-AS-DT: novel genes in the BDNF locus.

Divergent transcription from bidirectional promoters is frequently observed in eukaryotic genomes, but the biological relevance of divergent RNA transcripts (DT) is unknown. We identified and characterized BDNF-DT, a novel DT gene, and BDNF-AS-DT, a novel readthrough gene, in the locus containing BDNF, a gene with key roles in neuronal development, differentiation, and synaptic plasticity. BDNF-DT is independent from the known BDNF antisense (BDNF-AS), and its expression is developmentally regulated and positively correlated with BDNF in human postmortem dorsolateral prefrontal cortex (DLPFC). BDNF-DT and BDNF-AS-DT expression increase after induced depolarization, but the temporal dynamics follow expression of BDNF, suggesting a regulatory role. Moreover, CRISPR-mediated upregulation of BDNF in human neural progenitor cells drives BDNF-DT expression. Finally, BDNF-DT shows higher expression in DLPFC from patients diagnosed with schizophrenia compared to neurotypical controls, and genetically predicted lower expression of the BDNF-AS-DT readthrough transcript is associated with schizophrenia and with the schizophrenia-associated C allele of the rs6265 single-nucleotide polymorphism. These findings identify BDNF-DT and BDNF-AS-DT as novel, low-abundance genes that show coordinated expression with BDNF and association with schizophrenia risk, though their biological significance requires further validation given detection limitations and the need to establish causal roles.

Humans↗
PubMed2004

Fitness and life-history traits of the two major mitochondrial DNA haplotypes of Drosophila subobscura.

Mitochondrial DNA restriction site analyses on natural populations of Drosophila subobscura have proved the existence of two common, coexisting haplotypes (I and II), as well as a set of less frequent ones derived from them. To explain this distribution, experiments to date point practically to all possible genetic mechanisms being involved in the changes of gene frequencies (cytonuclear coadaptation, direct natural selection on mtDNA and genetic drift). In an attempt to find differences that help to understand the dynamics of these haplotypes and to detect the effect of selection, we measured certain fitness components and life-history traits (egg-larva and larva-adult viabilities and developmental times, longevity, resistance to desiccation and optimal density) of the two main haplotypes I and II when maintained in laboratory population cages. As a general trend, haplotype II showed a higher net fitness than haplotype I, which explains the superiority of haplotype II over haplotype I in experimental populations but not their coexistence in nature, where additional factors must be considered.

Animals↗
PubMed1999

Strict regulation of c-Raf kinase levels is required for early organogenesis of the vertebrate inner ear.

Regulation of organogenesis involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. Here we have investigated the pattern of expression of c-Raf kinase in the inner ear during early developmental stages and the consequences of manipulating c-Raf levels by misexpression of c-raf viral vectors in organotypic cultures of otic vesicle explants. We found that otic vesicles expressed c-Raf and its level remained constant during embryonic days 2 and 3 (E2-E3). c-Raf activity was increased in response to insulin like growth factor-I (IGF-I) and the activation by IGF-I of the c-Raf kinase pathway was a requirement to turn on cell proliferation in the otic vesicle. Overexpression of c-raf in E2.5 explants increased the proliferative response to low serum and IGF-I and blocked differentiation induced by retinoic acid. The increase in c-Raf levels also prevented nerve growth factor (NGF)-dependent induction of programmed cell death. Consistent with these results, the expression of a dominant negative c-Raf mutant potentiated retinoic acid action and decreased the rate of cell proliferation. We conclude that a strict control of c-Raf levels is essential for the co-ordination of the biological processes that operate simultaneously during early inner ear development.

Animals↗
PubMed2005

DSP1, a Drosophila HMG protein, is involved in spatiotemporal expression of the homoeotic gene Sex combs reduced.

BACKGROUND INFORMATION: The Pc-G (Polycomb group) and trx-G (trithorax group) genes play a key role in the regulation of the homoeotic genes. The homoeotic gene Scr (Sex combs reduced) contained in the Antennapedia complex specifies segmental identity of the labial and prothoracic segments in Drosophila. Regulation of Scr requires the action of different enhancer elements spread over several kilobases. We previously identified an HMGB (high mobility group)-like protein DSP1 (dorsal switch protein 1), which works like a trx-G protein for the normal Scr expression. RESULTS: In the present study, we attempted to characterize the regulatory sequences involved in the maintenance of the Scr activation by DSP1. We report here, using a transgenic line for the Scr10.0XbaI-regulatory element, that lack of DSP1 affects the function of a reporter gene in legs' imaginal discs but not in embryos. We show by immunolocalization that DSP1 is recruited on polytene chromosomes to the insertion site of the transgene. Moreover, using chromatin immunoprecipitation experiments, we identify two regions of 1 kb in Scr10.0XbaI as the main DSP1 targets. CONCLUSION: These results provide strong evidence that the Scr gene expression is influenced by direct interaction between DSP1 and two Scr regulation elements. In addition, our results show that this interaction undergoes dynamic changes during development.

Animals↗
PubMed1998

Examining the role of auditory sensitivity in the developmental weighting shift.

Studies comparing children's and adults' labeling of speech stimuli have repeatedly shown that children's phonological decisions are more strongly related to portions of the signal that involve rapid spectral change (i.e., formant transitions) and less related to other signal components than are adults' decisions. Such findings have led to a model termed the Developmental Weighting Shift, which suggests that children initially assign particularly strong weight to formant transitions to help delimit individual words in the continuous speech stream but gradually modify these strategies to be more like those of adults as they learn about word-internal structure. The goal of the current study was to test a reasonable alternative: that these apparent age-related differences in perceptual weighting strategies for speech are instead due to age-related differences in auditory sensitivity. To this end, difference limens (DLs) were obtained from children (ages 5 and 7 years) and adults for three types of acoustic properties: dynamic-spectral, static-spectral, and temporal. Two testable hypotheses were offered: Labeling results could reflect either absolute differences in sensitivity between children and adults or relative differences in sensitivity within each group. Empirical support for either hypothesis would indicate that apparent developmental changes in perceptual weighting strategies are actually due to developmental changes in auditory sensitivity to acoustic properties. Results of this study contradicted predictions of both hypotheses, sustaining the suggestion that children's perceptual weighting strategies for speech-relevant acoustic properties change as they gain experience with a native language.

Age Factors↗
PubMed2006

Population regulation of a classical biological control agent: larval density dependence in Neochetina eichhorniae (Coleoptera: Curculionidae), a biological control agent of water hyacinth Eichhornia crassipes.

The release of classical biological control agents has reduced the economic, environmental and social problems caused by water hyacinth, Eichhornia crassipes; however, additional control measures are needed in some locations. Water hyacinth plants were treated with different densities of eggs of the weevil Neochetina eichhorniae Warner, one of the main control agents, under different nutrient regimes in a controlled experiment. Plants were destructively sampled and the development of N. eichhorniae was assessed. The survival of first and second instars declined as larval density increased. Plant nutrient status did not directly affect the mortality rate of larvae, but at higher nutrient concentrations larvae developed faster and were larger at a given developmental stage. It is argued that the density dependence operating in N. eichhorniae occurs through an interaction between young larvae and leaf longevity. Consequently, events which disrupt water hyacinth leaf dynamics, e.g. frost or foliar herbicides, will have a disproportionately large effect on the control agents and may reduce the level of control of the host.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Microbial modulation of innate defense: goblet cells and the intestinal mucus layer.

The gastrointestinal epithelium is covered by a protective mucus gel composed predominantly of mucin glycoproteins that are synthesized and secreted by goblet cells. Changes in goblet cell functions and in the chemical composition of intestinal mucus are detected in response to a broad range of luminal insults, including alterations of the normal microbiota. However, the regulatory networks that mediate goblet cell responses to intestinal insults are poorly defined. The present review summarizes the results of developmental, gnotobiotic, and in vitro studies that showed alterations in mucin gene expression, mucus composition, or mucus secretion in response to intestinal microbes or host-derived inflammatory mediators. The dynamic nature of the mucus layer is shown. Available data indicate that intestinal microbes may affect goblet cell dynamics and the mucus layer directly via the local release of bioactive factors or indirectly via activation of host immune cells. A precise definition of the regulatory networks that interface with goblet cells may have broad biomedical applications because mucus alterations appear to characterize most diseases of mucosal tissues.

Animals↗