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Results for “Developmental programming”

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PubMed2005

Statistical analysis of data in support of the Barker hypothesis, advantages of using random effects regression model in hierarchical data.

In a recent note by Walters and Edwards (2004), the authors argued that summary statistics should be used in analysing hierarchical data from our earlier analysis of a rat model of developmental programming and the Barker hypothesis (Kwong et al., 2000, 2004). We reiterate here why such a view is inappropriate. Hierarchical data merits multilevel analysis using a 'random effects' model to enable estimation of variances at different levels and easy assessment of other parameters in a complex data structure.

Analysis of Variance↗

PubMed2004

Cryptic bracts exposed: insights into the regulation of leaf expansion.

Arabidopsis is unusual in producing flowers that are not subtended by specialized leaves, called floral bracts. Writing in Development, Dinneny et al. and Ohno et al. show that gain-of-function mutations of the JAGGED transcription factor produce bracts, and provide evidence that this gene plays a key role in a developmental program that regulates the size and shape of all leaves and leaf-homologs.

Arabidopsis↗

PubMedDate not supplied

Relationships between Müller cells and neurons in a primitive tetrapod, the Australian lungfish.

We recently proposed a model of cytogenesis which assumes that primitive ancestral mammals and premammalian vertebrates had a retinal composition that consisted of about seven neurons per Müller cell, comprising 1-2 cone photoreceptors, 1-2 rod photoreceptors, 2-3 bipolar cells, 1-2 amacrine cells, less than 1 ganglion cell, and less than 1 horizontal cell (Reichenbach & Robinson, 1995). The Australian lungfish (Neoceratodus forsteri) closely resembles the lobe-finned ancestors of land vertebrates, and has an extremely plesiomorphic nervous system. The present study, therefore, has examined the relative frequencies of retinal neurons and Müller cells (identified by immunolabelling for glutamine synthetase) in the lungfish retina. It was found that for each Müller cell there is an average of 1.9 cone photoreceptors, 1.7 rod photoreceptors, 3.1 amacrine/bipolar/horizontal cells, and 0.6 ganglion cells; amounting to a ratio of 7.3 neurons per Müller cell. These results support our conjecture that the sequence of cytogenesis in mammals is constrained by a developmental program that predates the evolution of mammals. The study also provides the first detailed morphological descriptions of lungfish Müller cells and their relationship with adjacent neurons. It was found that individual Müller cells in lungfish have a volume (more than 12,000 microns3) that is an order of magnitude higher than in mammals, yet the proportion of total retinal volume occupied by these cells (20%) is very similar.

Animals↗

PubMed2000

Developmental psychopathology: concepts and challenges.

The defining features of developmental psychopathology concepts include attention to the understanding of causal processes, appreciation of the role of developmental mechanisms, and consideration of continuities and discontinuities between normality and psychopathology. Accomplishments with respect to these issues are reviewed in relation to attachment disorders, antisocial behavior, autism, depressive disorder, schizophrenia, and intellectual development. Major research challenges remain in relation to measurement issues, comorbidity, gender differences, cognitive processing, nature-nurture interplay, heterotypic continuity, continuities between normal variations and disorders, developmental programming, and therapeutic mechanisms in effective treatments.

Child↗

PubMed2000

Psychosocial influences: critiques, findings, and research needs.

Nongenetic factors have a major influence on psychopathology. Knowledge on specific psychosocial risk and protective mechanisms is more limited because of inadequate attention to measurement issues, person effects on the environment, and the possibility of genetic mediation. Nevertheless, a range of research strategies may be used to provide rigorous tests of causal hypotheses; these have shown the importance of environmentally mediated risks. Challenges for the future include greater use of such research strategies, improved measures of psychosocial risks that can be applied to large samples, investigation of origins of risks, identification of causes of time trends in levels of psychopathology, delineation of psychosocial effects on lifetime liability, understanding of environmental effects on the organism, appreciation of processes involved in developmental programming, and understanding of individual differences in susceptibility.

Humans↗

PubMed1989

Regulation of collagen gene expression in 3T3-L1 cells. Effects of adipocyte differentiation and tumor necrosis factor alpha.

An early feature in the development of adipocytes from fibroblast-like precursor cells is the biogenesis of an extracellular basement membrane (Napolitano, 1963; Kuri-Harcuch et al., 1984). Interactions between components of the basement membrane (e.g., collagens) and the surfaces of differentiating adipocytes are thought to regulate subsequent phases of the developmental program. Since fibroblasts principally secrete type I and III collagens whereas type IV collagen is abundant in basement membrane, it appears that a switch in collagen gene expression is a key element in adipocyte differentiation. Little is known about the mechanisms underlying differentiation-dependent changes in collagen expression or the effects of the potent lipolytic cytokine TNF-alpha on collagen mRNA accumulation in preadipocytes and adipocytes. In this study, 3T3-L1 preadipocytes were found to express mRNAs encoding type I, III, and IV procollagens. When 3T3-L1 cells were stimulated to differentiate into adipocytes, the relative concentrations of type I and type III procollagen mRNAs declined by 80-90%. Parallel decreases in the rates of transcription of the procollagen I and procollagen III genes appear to account for the diminished levels of these mRNAs. In contrast, the relative rate of transcription of the procollagen IV gene increased 2.6-fold during adipocyte development. As a consequence, the abundance of type IV procollagen transcripts was elevated in adipocytes. Tumor necrosis factor alpha (TNF-alpha) is a cytokine that stimulates lipolysis, an apparent "dedifferentiation" of adipocytes, and inhibits transcription of certain adipocyte-specific genes. The effects of TNF-alpha on collagen mRNA levels were dependent upon the state of differentiation of 3T3-L1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1997

Neurotrophic 3,9-bis[(alkylthio)methyl]-and-bis(alkoxymethyl)-K-252a derivatives.

A series of 3,9 disubstituted [(alkylthio)methyl]- and (alkoxymethyl)-K-252a derivatives was synthesized with the aim of enhancing and separating the neurotrophic properties from the undesirable NGF (trk A kinase) and PKC inhibitory activities of K-252a. Data from this series reveal that substitution in the 3- and 9-positions of K-252a with these groups reduces trk A kinase inhibitory properties approximately 100- to > 500-fold while maintaining or in certain cases enhancing the neurotrophic activity. From this research, 3,9-bis[(ethylthio)methyl]-K-252a (8) was identified as a potent and selective neurotrophic agent in vitro as measured by enhancement of choline acetyltransferase activity in embryonic rat spinal cord and basal forebrain cultures. Compound 8 was found to have weak kinase inhibitory activity for trk A, protein kinase C1 protein kinase A, and myosin light chain kinase. On the basis of the in vitro profile, 8 was evaluated in in vivo models suggestive of neurological diseases. Compound 8 was active in preventing degeneration of cholinergic neurons of the nucleus basalis magnocellularis (NBM) and reduced developmentally programmed cell death (PCD) of female rat spinal nucleus of the bulbocavernosus motoneurons and embryonic chick lumbar motoneurons.

Animals↗

PubMed1998

Structural analysis of the nit2/nit1/nit3 gene cluster encoding nitrilases, enzymes catalyzing the terminal activation step in indole-acetic acid biosynthesis in Arabidopsis thaliana.

A 13.8 kb DNA sequence containing the promoters and the structural genes of the Arabidopsis thaliana nit2/nit1/nit3 gene cluster has been isolated and characterized. The coding regions of nit2, nit1 and nit3 spanned 1.9, 1.8 and 2.1 kb, respectively. The architecture of the three genes is highly conserved. Each isoform consists of five exons separated by four introns. The introns are very similar with respect to size and position, but differ considerably in sequence composition. In contrast to the coding sequences the three promoters are very different in sequence, size and in their repertoire of cis elements, suggesting differential regulation of the three nitrilase isoenzymes by the developmental program of the plant and by diverse environmental factors. The nit1 promoter was subjected to analysis in planta. Translational fusions placing the nit1 full-length promoter and a series of 5'-deletion fragments in front of the uidA gene encoding beta-glucuronidase (GUS) were used for Agrobacterium tumefaciens-mediated transformation of Nicotiana tabacum. GUS expression was highest in fully expanded leaves and in the shoot apex as well as in the apices of developing lateral buds, whereas the GUS activity displayed by developing younger leaflets was restricted to the tips of the expanding leaves. Within the root tissue GUS expression was restricted to the root tips and the tips of newly forming lateral roots. Structural features of the nitrilase gene family and nitrilase gene expression patterns are discussed in context with current knowledge of auxin biosynthesis and auxin effects on different tissues.

Aminohydrolases↗

PubMed1999

Structure and functional analysis of the 26S proteasome subunits from plants.

As initial steps to define how the 26S proteasome degrades ubiquitinated proteins in plants, we have characterized many of the subunits that comprise the proteolytic complex from Arabidopsis thaliana. A set of 23 Arabidopsis genes encoding the full complement of core particle (CP) subunits and a collection encoding 12 out of 18 known eukaryotic regulatory particle (RP) subunits, including six AAA-ATPase subunits, were identified. Several of these 26S proteasome genes could complement yeast strains missing the corresponding orthologs. Using this ability of plant subunits to functionally replace yeast counterparts, a parallel structure/function analysis was performed with the RP subunit RPN 10/MCB1, a putative receptor for ubiquitin conjugates. RPN10 is not essential for yeast viability but is required for amino acid analog tolerance and degradation of proteins via the ubiquitin-fusion degradation pathway, a subpathway within the ubiquitin system. Surprisingly, we found that the C-terminal motif required for conjugate recognition by RPN10 is not essential for in vivo functions. Instead, a domain near the N-terminus is required. We have begun to exploit the moss Physcomitrella patens as a model to characterize the plant 26S proteasome using reverse genetics. By homologous recombination, we have successfully disrupted the RPN10 gene. Unlike yeast rpn10delta strains which grow normally, Physcomitrella rpn10delta strains are developmentally arrested, being unable to initiate gametophorogenesis. Further analysis of these mutants revealed that RPN10 is likely required for a developmental program triggered by plant hormones.

Arabidopsis↗

PubMed2002

Regulation of photosynthesis during Arabidopsis leaf development in continuous light.

Previous investigations in our laboratory have shown that leaf developmental programming in tobacco is regulated by source strength. One hypothesis to explain how source strength is perceived is that hexokinase acts as a sensor of carbohydrate flux to regulate the expression of photosynthetic genes, possibly as a result of sucrose cycling through acid invertase and hexokinase. We have turned to Arabidopsis as a model system to study leaf development and have examined various photosynthetic parameters during the ontogeny of a single leaf on the Arabidopsis rosette grown in continuous light. We found that photosynthetic rates, photosynthetic gene expression, pigment contents and total protein amounts attain peak levels early in the expansion phase of development, then decline progressively as development proceeds. In contrast, the flux of (14)CO(2) into hexoses increases modestly until full expansion is attained, then falls in the fully expanded leaf. Partitioning of carbon into hexoses versus sucrose increases until full expansion is attained, then falls. The in vitro activities of hexokinase, vacuolar acid invertase, and cell wall acid invertase do not change until the late stages of senescence, when they increase markedly. At this time there are also dramatic increases in hexose pool sizes and in senescence-associated gene (SAG) expression. Taken together, our results suggest that invertase and hexokinase activities do not control the partitioning of label into hexoses during development. We conclude that our data are not readily compatible with a simple model of leaf development, whereby alterations in photosynthetic rates are mediated directly by hexose flux or by hexose pool sizes. Yet, these factors might contribute to the control of gene expression.

Journal Article↗

PubMed2002

The 21-day postnatal rat ventricular cardiac muscle cell in culture as an experimental model to study adult cardiomyocyte gene expression.

The purpose of this study was to develop and characterize a cardiomyocyte culture system for use as an experimental model to study the mechanism(s) by which cardiac muscle cells permanently exit the cell cycle during early neonatal life. Ventricular cardiomyocytes, isolated by retrograde perfusion of hearts from 21-day-old and adult rats, were compared through 10 days of culture. Expression patterns of genes encoding developmentally programmed proteins were determined to be similar between cardiomyocytes cultured from 21-day-old and adult rats, using the reverse transcription polymerase chain reaction. A lacZ-expressing reporter gene was used to test the efficiency of gene delivery in cultured cardiomyocytes. Transfections using cationic liposomes yielded 24+/-7, 25+/-7 and 10+/-1% cardiomyocytes positive for beta-galactosidase activity in cultured 1-day, 21-day and adult cardiomyocytes, respectively. Direct needle microinjection resulted in 48+/-7, 35+/-6 and 37+/-5% cardiomyocytes positive for enzymatic activity in 1-day, 21-day and adult cardiomyocytes, respectively. Cell cycle-specific cDNA arrays were used to analyze the expression pattern of cell cycle-related genes in 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- and non-TPA-treated cultured 21-day cardiomyocytes. Based on the similarity of cultured 21-day to adult ventricular cardiomyocytes and their high transfection efficiencies, we propose the use of cultured cardiomyocytes from 21-day-old rat ventricles as an experimental model system for the study of adult cardiomyocyte gene expression and cell cycle machinery.

Animals↗

PubMed2002

Induction of oligodendrocyte fate during the formation of the vertebrate neural tube.

The development of the central nervous system (CNS) comprises a series of inductive and transforming events that includes rostro-caudal and dorso-ventral patterning, neuroglial specification and extensive cell migration. The patterning of the neural tube is also characterized by the transcription of specific genes, which encode for morphogens and transcription factors essential for cell fate specification. The generation of oligodendrocytes, the myelin forming glial cells in the CNS, appears to be restricted to specific domains localized in the ventral neuroepithelium. Signaling mediated by sonic hedgehog (Shh) seems to command the early phase of the specification of uncommitted neural stem cells into the oligodendroglial lineage. Once generated, oligodendrocyte progenitors have to follow a developmental program that involves changes in cell morphology, migratory capacity and sensitivity to extracellular trophic factors before becoming mature myelinating cells. This minireview aims to discuss molecular aspects of the early induction of oligodendroglial fate during the formation of the CNS.

Animals↗

PubMedDate not supplied

Neuregulin: an activity-dependent synaptic modulator at the neuromuscular junction.

Synaptic activity in the form of neurotransmitter release and postsynaptic depolarization is a prime motive force that guides synaptic development throughout the nervous system. The molecular basis of how synaptic activity is converted into structural changes that build and maintain synapses is a key question that has recently become focused on regulatory factors that act on tyrosine kinase receptors on both sides of the synaptic interface. The neuregulins are such a family of growth and differentiation factors that exist as both membrane-bound and soluble forms through alternatively splicing. Neuregulin functions to promote the local expression of acetylcholine receptors at neuromuscular synapses and therefore has the potential to strengthen specific synaptic connections. Recent evidence suggests that synaptic activity at the neuromuscular junction is coupled to presynaptic neuregulin release through an indirect mechanism acting through the postsynaptic expression of neurotrophic factors. At early stages of development, this could potentiate the stability of more active synapses. Later in development, heparin-binding forms of neuregulin accumulate to high levels in the synaptic basal lamina through the developmentally programmed expression of heparan sulfate proteoglycans, thus providing a sustained source of neuregulin to the most active synapses.

Animals↗

PubMed2003

Fertilization induces strong accumulation of a histone deacetylase (HD2) and of other chromatin-remodeling proteins in restricted areas of the ovules.

Fertilization triggers a unique and complex developmental program leading to embryogenesis and seed set. Recently, mutations affecting chromatin-remodeling enzymes in plants have shown their key roles in development as demonstrated before in animal cells. Using a negative selection screen to isolate genes expressed in ovary tissues upon fertilization, we have identified a histone deacetylase gene (named ScHD2a ) of the plant-specific HD2 family, which is predominantly expressed in ovaries of the self-incompatible species Solanum chacoense. The ScHD2a is the probable orthologue of the Arabidopsis thaliana AtHD2a gene, which upon antisense suppression leads to aborted seeds formation. Transcription of the ScHD2a gene is strongly triggered by fertilization and transcripts accumulate predominantly in the micropylar region of the ovule's integument. Interestingly, this fertilization-induced accumulation pattern was also observed for other genes involved in transcriptional repression but not for a MYST-family histone acetyltransferase. The strong increase in ScHD2a mRNA levels in ovules after fertilization suggests an important and localized role for transcriptional repression in seed development, and indicates why silencing of the AtHD2a gene leads to aborted seed formation.

Acetyltransferases↗

PubMed2002

Transdifferentiation and nuclear reprogramming in hematopoietic development and neoplasia.

Cell transplantation and tissue regeneration studies indicate a surprisingly broad developmental potential for lineage-committed hematopoietic stem cells (HSCs). Under these conditions HSCs transition into myocytes, neurons, hepatocytes or other types of nonhematopoietic effector cells. Equally impressive is the progression of committed neuronal stem cells (NSCs) to functional blood elements. Although critical cell-of-origin issues remain unresolved, the possibility of lineage switching is strengthened by a few well-controlled examples of cell-type conversion. At the molecular level, switching probably initiates from environmental signals that induce epigenetic modifications, resulting in changes in chromatin configuration. In turn, these changes affect patterns of gene expression that mediate divergent developmental programs. This review examines recent findings in nuclear reprogramming and cell fusion as potential causative mechanisms for transdifferentiation during normal and malignant hematopoiesis.

Animals↗

PubMed2003

Lymphoid microenvironment in the gut for immunoglobulin A and inflammation.

Signaling through lymphotoxin beta receptor (LTbetaR) initiates the unfolding of a host of developmental programs ranging from the organogenesis of lymph nodes and Peyer's patches (PPs) to the coordination of splenic microarchitecture. While investigating an alternative pathway to immunoglobulin A (IgA) production, it was uncovered that LTbetaR signaling in the lamina propria (LP) stroma orchestrates the coordinated expression of key chemokines and adhesion molecules, creation of a cytokine milieu, and stroma development that facilitates robust IgA production independent of secondary lymphoid structures. Simultaneously, this same infrastructure can be commandeered by autoreactive T cells to organize both the acute destruction of the intestinal mucosa and chronic intestinal inflammation via the ligands for LTbetaR. The ability to modulate LTbetaR signaling may alternatively permit the suppression of autoimmune responses and augmentation of gut defenses.

Animals↗

PubMed1989

Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development.

The mouse homoeobox-containing genes exhibit temporally and spatially specific patterns of expression in embryonic and adult tissues and are thought to be important in regulation of development and cellular differentiation, perhaps by mechanisms analogous to homoeotic genes in Drosophila melanogaster. There has been no direct demonstration that expression of these mammalian genes can affect developmental processes, however. Hox-1.4, like other mouse homoeobox-containing genes, has been shown to be expressed in specific regions of the mid-gestation embryo, but is unique in that its highest level of expression in the adult animal is restricted to developing male germ cells. We have introduced a construct carrying the mouse Hox-1.4 gene into the germ line of mice to begin to identify the cis-acting elements required for proper expression and to assess the consequences of increasing Hox-1.4 gene expression. The construct was designed to produce normal Hox-1.4 protein from transcripts that are distinguishable from the products of the endogenous gene. The integrated transgene seemed to exhibit the appropriate tissue specificity of expression, but transcript levels were elevated in certain tissues, particularly the embryonic gut. This overexpression correlated with changes in the normal developmental program of the gut, resulting in an inherited abnormal phenotype known as megacolon.

Animals↗

PubMed2000

Engineering stability in gene networks by autoregulation.

The genetic and biochemical networks which underlie such things as homeostasis in metabolism and the developmental programs of living cells, must withstand considerable variations and random perturbations of biochemical parameters. These occur as transient changes in, for example, transcription, translation, and RNA and protein degradation. The intensity and duration of these perturbations differ between cells in a population. The unique state of cells, and thus the diversity in a population, is owing to the different environmental stimuli the individual cells experience and the inherent stochastic nature of biochemical processes (for example, refs 5 and 6). It has been proposed, but not demonstrated, that autoregulatory, negative feedback loops in gene circuits provide stability, thereby limiting the range over which the concentrations of network components fluctuate. Here we have designed and constructed simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli and we show the gain of stability produced by negative feedback.

DNA Transposable Elements↗