SEARCH · PubMed Health

Results for “Developmental programming”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,171 records · Page 65Linked to original sources

PubMed2000

Transcriptional and post-transcriptional regulation of a brain growth protein: regional differentiation and regeneration induction of GAP-43.

During axonal regeneration synthesis of different growth-associated proteins is increased. As yet there is no clear picture of the specific contribution made by the transcriptional and post-transcriptional machinery that provides the gene products necessary for process outgrowth. Here we focus our study on the transcriptional processes in neurons by using intron-directed in situ hybridization to the primary transcript of a brain growth protein GAP-43. In most brain regions, levels of primary transcript expression of GAP-43 were highly correlated with levels of its mRNA. However, there were notable dissociations: in hippocampal granule cells, high levels of primary transcript were evident yet no GAP-43 mRNA was detected. In locus coeruleus the reverse was true; there were high levels of GAP-43 mRNA but no detectable primary transcript. A primary transcript antitermination mechanism is proposed to explain the first dissociation, and a post-transcriptional mRNA stabilization mechanism to explain the second. Transcriptional activation during nerve regeneration was monitored by assessing primary transcript induction of GAP-43 in mouse facial motor neurons. This induction, as well as its mRNA, was restricted to the side of the facial nerve crush. Increases were first observed at 24 h with a rapid increase in both measures up to 3 days. To our knowledge, this is the first in vivo evidence demonstrating transcriptional activation of a brain growth protein in regenerating neurons. The present study points to the GAP-43 transcriptional mechanism as a key determinant of GAP-43 synthesis. Along with the recruitment of post-transcriptional mechanisms, such synthesis occurs in response to both intrinsic developmental programs and extrinsic environmental signals.

Animals↗

PubMed2000

Morphological and biochemical re-evaluation of the process of cavitation in the rat knee joint: cellular and cell strata alterations in the interzone.

To assess the contribution of apoptosis to the mechanism of synovial joint cavitation, and to clarify morphological cellular changes during cavitation, we investigated the development of the rat knee joint by light and electron microscopy, TUNEL methods, and electrophoresis of DNA fragments. Although cavitation occurred within the interzone, which consists of 2 outer and a middle layer termed the intermediate zone, no morphological or biochemical signs of cell death, in particular apoptosis, were seen in the interzone at any embryonic stage. Microscopic and ultrastructural alterations affecting cell differentiation were clearly observed in the interzone, i.e. mesenchymal cells gradually showed elongation, cytoplasmic vacuolation and pyknosis in the intermediate zone where the elongated cells were arranged in parallel in some strata. Some of these cells were further flattened into spindle cells and the number of strata decreased to 2. The rest of the cells were incorporated secondarily into the outer layers, becoming chondroblasts. Collagen fibrils were arranged in a network structure in the outer layers, which obviously differed from the directional pattern parallel to the long axis of elongated cells in the intermediate zone. In addition, the density of collagen fibrils was higher in the outer layers than in the intermediate zone. During cavitation, the initial separation was detected between the elongated cells in the intermediate zone in paraffin sections at E16.5 and the spindle cells in epoxy sections at E18.5. The spindle cells lining the cavity, namely, the surfaces of the epiphysis and meniscus, finally became chondrocytes. The diminution of proteoglycans and collagen fibrils and the synthesis of hyaluronan in the extracellular matrix are now generally believed to be parts of the mechanism for cavitation based on the concept of 'loss of cohesion'. The microscopic and ultrastructural alterations in the interzone seemed to reflect differences in the arrangement and density of collagen fibrils and the developmental condition of the extracellular matrix between layers. Also it did not seem likely that these alterations inhibit the synthesis of hyaluronan at the presumptive joint line because this synthesis takes place at the plasma membrane. Separation between spindle cells should therefore represent the mechanism for developmentally programmed cavitation. Reorganization of the extracellular matrix is probably necessary for the cellular metamorphoses in the interzone involved in the process of cavitation.

Animals↗

PubMed2000

Modulation of GABA(A) receptor subunit mRNA levels in olivocerebellar neurons of purkinje cell degeneration and weaver mutant mice.

In olivocerebellar circuits, changes in the subunit composition of GABA(A) receptors occur at a time of extensive synaptic remodeling. In the deep cerebellar nuclei, GABA(A) receptor alpha1, beta2, and gamma2 subunit mRNA expression increases throughout neonatal development, whereas in the inferior olivary complex, the perinatal combination of alpha3, alpha5, beta3, and gamma2 mRNAs switches to the adult combination of alpha2, alpha4, beta3 and gamma1 during postnatal week 2. In situ hybridization was used to examine changes in subunit expression in the olivocerebellar nuclei of Purkinje cell degeneration and weaver mutant mice. In Purkinje cell degeneration, subunit transcripts decreased below control levels in olivary neurons; however, alpha1, beta2, and gamma2 transcript levels were slightly increased in the medial nucleus of the deep cerebellar nuclei. In weaver olivary neurons, although the switch from early- to late-onset subunit mRNAs occurred as in normal mice, transcript levels were differentially modulated by the mutation. Our studies indicate that major alterations in synaptic connectivity do not prevent developmentally programmed switches in GABA(A) receptor gene expression but can modulate the timing and level of transcript expression in afferent and efferent neurons.

Animals↗

PubMed2003

4-hydroxynonenal contributes to NGF withdrawal-induced neuronal apoptosis.

Reactive oxygen species are a necessary triggering event for apoptosis of sympathetic neurons after nerve growth factor (NGF) withdrawal. Reactive oxygen species can lead to the generation of 4-hydroxynonenal (HNE), a highly reactive aldehyde that forms adducts with proteins. This covalent modification can activate or inhibit signal transduction pathways involved in the induction of apoptosis. This process may be clinically relevant because HNE-adduct immunoreactivity increases in several disease states. Here we evaluate the role of HNE-adducts in sympathetic neurons undergoing NGF-deprivation-induced apoptosis, a model of developmental programmed cell death. We show that HNE-adduct immunoreactivity is dramatically increased after NGF-withdrawal in an NADPH oxidase-dependent manner. Moreover, HNE-adducts appear to contribute to NGF-deprivation-induced apoptotic signal transduction because microinjected HNE-adduct antiserum protects sympathetic neurons from NGF withdrawal. In conclusion, this report suggests the direct contribution of endogenously generated HNE in the stimulation of apoptotic signal transduction in neurons.

Aldehydes↗

PubMed2005

[Reprogramming and epigenesis].

The fact that the nucleus of a differentiated somatic cell can be reprogrammed in order to sustain embryonic development is now well established. Experiments of somatic cell nuclear transfer (cloning) have proved that a foreign nucleus introduced into an enucleated oocyte can give rise to physiologically normal offsprings, with a normal lifespan. Such evidence of genome expression plasticity is also observed experimentally with heterokaryons, created by the fusion or the nuclear transfer between two somatic cells, where differentiated nuclei are able to express genes characteristic of the host cell. However, the epigenetic mechanisms that permit nuclear plasticity remain poorly understood. In this paper we present the main evidences showing important modifications of the large scale organisation of chromosomal domains and of the DNA methylation pattern upon nuclear transfer and during the first cleavages. These modifications of epigenetic marks, brought by an intimate contact between the chromatin and the recipient oocyte cytoplasmic factors, appear essential for further development. They are established over the first cell cycles of development. The onset of embryonic genome activation and the first cellular differentiation events that occur over the implantation period are two additional check-points of reprogramming that appear to be also highly dependent on epigenetic alterations. Beyond those stages, defective placental functions might be directly responsible for the fetal and postnatal physiopathologies frequently observed in cloned animals. No direct link between preimplantation reprogramming defaults, placental dysfunctions and low development to term has been established yet. The epigenetics studies which are now used to characterise loci specific and probably genotype dependent alterations in cloned animals of different species will provide invaluable help to define the role of epigenesis in the achievement of a developmental program.

Animals↗

PubMedDate not supplied

Trophoblastic cell lines generated from tumour necrosis factor receptor-deficient mice reveal specific functions for the two tumour necrosis factor receptors.

In mice and humans, expression of the tumour necrosis factor receptor-1 (TNF-R1) gene in placental trophoblast cells is constitutive whereas expression of the TNF-R2 gene is developmentally programmed. In order to study the individual functions of TNF-R1 and -R2 in this lineage, cell lines were generated from placental explants of homozygous matings of gestation day 10 outbred mice (Swiss-Webster), TNF-R1-deficient (TNF-R1-/-) and TNF-R2-/- transgenic mice as well as the background strain for the TNF-R2-/- mice (WT, C57BL/6x129). All of the cells exhibited trophoblast markers; they contained cytokeratin intermediate filaments, expressed alkaline phosphatase activity and displayed transferrin receptors, but were negative for vimentin filaments and the macrophage marker, F4/80. Analysis of DNA by polymerase chain reaction demonstrated the expected TNF-R genotype in each line. In experiments testing the effects of recombinant mouse TNF-alpha (rmTNF-alpha) on viability and proliferation of the cell lines, rmTNF-alpha modestly but dose-dependently inhibited the growth of WT and TNF-R2-/- cells while having no effect on TNF-R1-/- cells. Actinomycin D-treated WT and, to a lesser extent, TNF-R2-/- cells, were more sensitive to growth inhibition than untreated cells whereas TNF-R1-/- cell responses remained unchanged. These data indicated that rmTNF-alpha inhibits growth of trophoblastic cells through TNF-R1 and that newly synthesized protein(s) provide partial protection against toxicity. In contrast to the receptor species-specific effects on cell growth exerted by rmTNF-alpha, both TNF-R mediated inhibition of alkaline phosphatase activity. Collectively, the observations support the postulate that receptor expression is the key factor which determines the nature and extent of TNF-alpha effects on trophoblast cell growth and function.

Alkaline Phosphatase↗

PubMed2004

Initiation of lung immunity: the afferent limb and the role of dendritic cells.

The lung is the largest epithelial surface in the body and constitutes a major portal of entry for microorganisms. Dendritic cells (DCs) are bone marrow-derived cells that populate the respiratory tract from the nasal mucosa to the lung pleura. DCs are dexterous cells playing a role in both the innate and the adaptive immune responses. DCs can respond to dangers in the lung by immediately generating protective cytokines that stimulate natural killer (NK) cells to produce cytokines and kill targets. Direct (by pathogen recognition receptors) and indirect (by inflammatory cytokines) recognition of the infectious agent can also trigger signaling pathways in the DCs that activate an integrated developmental program called maturation, which transforms DCs into efficient antigen-presenting cells (APCs) for naive T cell stimulation. Furthermore, DCs play a role in generating effector B cells in the lymph nodes draining the lung. This review focuses on how DCs sense the health of the lung and translate messages regarding the lung microenvironment to cells of the innate and adaptive immune response to initiate effector functions to clear an invading microorganism [T helper 1 (Th1) or Th2 response] or generate tolerance [T regulatory (Tr), anergy, or deletion] to inhaled antigen when no danger is sensed.

Journal Article↗

PubMed2006

Crosstalk between auxin, cytokinins, and sugars in the plant cell cycle.

Plant meristems are utilization sinks, in which cell division activity governs sink strength. However, the molecular mechanisms by which cell division activity and sink strength are adjusted to a plant's developmental program in its environmental setting are not well understood. Mitogenic hormonal as well as metabolic signals drive and modulate the cell cycle, but a coherent idea of how this is accomplished, is still missing. Auxin and cytokinins are known as endogenous mitogens whose concentrations and timing, however, can be externally affected. Although the sites and mechanisms of signal interaction in cell cycle control have not yet been unravelled, crosstalk of sugar and phytohormone signals could be localized to several biochemical levels. At the expression level of cell cycle control genes, like cyclins, Cdks, and others, synergistic but also antagonistic interactions could be demonstrated. Another level of crosstalk is that of signal generation or modulation. Cytokinins affect the activity of extracellular invertases and hexose-uptake carriers and thus impinge on an intracellular sugar signal. With tobacco BY-2 cells, a coordinated control of cell cycle activity at both regulatory levels could be shown. Comparison of the results obtained with the root cell-representing BY-2 cells with literature data from shoot tissues or green cell cultures of Arabidopsis and Chenopodium suggests opposed and tissue-specific regulatory patterns of mitogenic signals and signal crosstalk in root and shoot meristems.

Arabidopsis↗

PubMed2004

BofA protein inhibits intramembrane proteolysis of pro-sigmaK in an intercompartmental signaling pathway during Bacillus subtilis sporulation.

Bacillus subtilis is a bacterium that undergoes a developmental program of sporulation in response to starvation. At the core of the program are sigma factors, whose regulated spatiotemporal activation controls much of the gene expression. Activation of pro-sigma(K) in the mother cell compartment involves regulated intramembrane proteolysis (RIP) in response to a signal from the forespore. RIP is a poorly understood process that is conserved in prokaryotes and eukaryotes. Here, we report a powerful system for studying RIP of pro-sigma(K). Escherichia coli was engineered to coexpress the putative membrane-embedded metalloprotease SpoIVFB with pro-sigma(K) and potential inhibitors of RIP. Overproduction of SpoIVFB and pro-sigma(K) in E. coli allowed accurate and abundant proteolytic processing of pro-sigma(K) with the characteristics expected for SpoIVFB acting as an intramembrane-cleaving protease (I-Clip). Coexpression of BofA in this system led to formation of a BofA-SpoIVFB complex and marked inhibition of pro-sigma(K) processing. Mutational analysis identified amino acids in BofA that are necessary for complex formation and inhibition of processing, leading us to propose that BofA inhibits SpoIVFB metalloprotease activity by providing a metal ligand, analogous to the cysteine switch mechanism of matrix metalloprotease regulation. The approach described herein should be applicable to studies of other RIP events and amenable to developing in vitro assays for I-Clips.

Bacillus subtilis↗

PubMed2004

Transcript profiling of early lateral root initiation.

At the onset of lateral root initiation in Arabidopsis thaliana, the phytohormone auxin activates xylem pole pericycle cells for asymmetric cell division. However, the molecular events leading from auxin to lateral root initiation are poorly understood, in part because the few responsive cells in the process are embedded in the root and are thus difficult to access. A lateral root induction system, in which most xylem pole pericycle cells were synchronously activated by auxin transport inhibition followed by auxin application, was used for microarray transcript profiling. Of 4,600 genes analyzed, 906 significantly differentially regulated genes were identified that could be grouped into six major clusters. Basically, three major patterns were discerned representing induced, repressed, and transiently expressed genes. Analysis of the coregulated genes, which were specific for each time point, provided new insight into the molecular regulation and signal transduction preceding lateral root initiation in Arabidopsis. The reproducible expression profiles during a time course allowed us to define four stages that precede the cell division in the pericycle. These early stages were characterized by G1 cell cycle block, auxin perception, and signal transduction, followed by progression over G1/S transition and G2/M transition. All these processes took place within 6 h after transfer from N-1-naphthylphthalamic acid to 1-naphthalene acetic acid. These results indicate that this lateral root induction system represents a unique synchronized system that allows the systematic study of the developmental program upstream of the cell cycle activation during lateral root initiation.

Cell Cycle↗

PubMed2005

Inference of combinatorial regulation in yeast transcriptional networks: a case study of sporulation.

Decomposing transcriptional regulatory networks into functional modules and determining logical relations between them is the first step toward understanding transcriptional regulation at the system level. Modules based on analysis of genome-scale data can serve as the basis for inferring combinatorial regulation and for building mathematical models to quantitatively describe the behavior of the networks. We present here an algorithm called modem to identify target genes of a transcription factor (TF) from a single expression experiment, based on a joint probabilistic model for promoter sequence and gene expression data. We show how this method can facilitate the discovery of specific instances of combinatorial regulation and illustrate this for a specific case of transcriptional networks that regulate sporulation in the yeast Saccharomyces cerevisiae. Applying this method to analyze two crucial TFs in sporulation, Ndt80p and Sum1p, we were able to delineate their overlapping binding sites. We proposed a mechanistic model for the competitive regulation by the two TFs on a defined subset of sporulation genes. We show that this model accounts for the temporal control of the "middle" sporulation genes and suggest a similar regulatory arrangement can be found in developmental programs in higher organisms.

Algorithms↗

PubMed2004

Cup is a nucleocytoplasmic shuttling protein that interacts with the eukaryotic translation initiation factor 4E to modulate Drosophila ovary development.

In Drosophila, the product of the fs (2)cup gene (Cup) is known to be crucial for diverse aspects of female germ-line development. Its functions at the molecular level, however, have remained mainly unexplored. Cup was found to directly associate with eukaryotic translation initiation factor 4E (eIF4E). In this report, we show that Cup is a nucleocytoplasmic shuttling protein and that the interaction with eIF4E promotes retention of the Cup protein in the cytoplasm. Cup is required for the correct accumulation and localization of eIF4E within the posterior cytoplasm of developing oocytes. We furthermore show that cup and eIF4E interact genetically, because a reduction in the level of eIF4E activity deteriorates the development and growth of ovaries bearing homozygous cup mutant alleles. Our results reveal a crucial role for the Cup-eIF4E complex in ovary-specific developmental programs.

Animals↗

PubMed2002

The mammalian oocyte orchestrates the rate of ovarian follicular development.

The development of both the mammalian oocyte and the somatic cell compartments of the ovarian follicle is highly coordinated; this coordination ensures that the ovulated oocyte is ready to undergo fertilization and subsequent embryogenesis. Disruption of this synchrony results in oocyte developmental failure. Communication between the oocyte and companion somatic cells is essential for successful development of both follicular compartments. However, it was not previously known whether one cell type, either the somatic or the germ cell compartment, determines the overall rate of follicular development. To test the hypothesis that the oocyte orchestrates the rate of follicle development, mid-sized oocytes isolated from secondary follicles were transferred back to primordial follicles, the earliest stage of follicular development. This transfer doubled the rate of follicular development and the differentiation of follicular somatic cells. Oocyte development in these accelerated follicles appeared normal; recovered oocytes were competent to undergo fertilization and embryonic development. These results demonstrate that oocytes orchestrate and coordinate the development of mammalian ovarian follicles and that the rate of follicular development is based on a developmental program intrinsic to the oocyte.

Animals↗

PubMed2006

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

Deltaproteobacteria↗

PubMed2000

Do lampreys have lymphocytes? The Spi evidence.

It is generally accepted that living jawless vertebrates (lampreys and hagfishes) lack the capability of mounting an adaptive immune response. At the same time, however, there are reports describing histological evidence for the presence in agnathan tissues of lymphocytes, the key players in adaptive immunity. The question therefore arises whether the cells identified morphologically as lymphocytes are true lymphocytes in terms of their genetic developmental program. In this study, evidence is provided that the lampreys express a member of the purine box 1 (PU.1)/spleen focus-forming virus integration B (Spi-B) gene family known to be critically and specifically involved in the differentiation of lymphocytes in jawed vertebrates. The lamprey gene is expressed in the lymphocyte-like cells of the digestive tract and inexplicably also in the ovary.

Amino Acid Sequence↗

PubMed2003

Development of teeth in chick embryos after mouse neural crest transplantations.

Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.

Animals↗

PubMed2001

Two recombination-dependent DNA replication pathways of bacteriophage T4, and their roles in mutagenesis and horizontal gene transfer.

Two major pathways of recombination-dependent DNA replication, "join-copy" and "join-cut-copy," can be distinguished in phage T4: join-copy requires only early and middle genes, but two late proteins, endonuclease VII and terminase, are uniquely important in the join-cut-copy pathway. In wild-type T4, timing of these pathways is integrated with the developmental program and related to transcription and packaging of DNA. In primase mutants, which are defective in origin-dependent lagging-strand DNA synthesis, the late pathway can bypass the lack of primers for lagging-strand DNA synthesis. The exquisitely regulated synthesis of endo VII, and of two proteins from its gene, explains the delay of recombination-dependent DNA replication in primase (as well as topoisomerase) mutants, and the temperature-dependence of the delay. Other proteins (e.g., the single-stranded DNA binding protein and the products of genes 46 and 47) are important in all recombination pathways, but they interact differently with other proteins in different pathways. These homologous recombination pathways contribute to evolution because they facilitate acquisition of any foreign DNA with limited sequence homology during horizontal gene transfer, without requiring transposition or site-specific recombination functions. Partial heteroduplex repair can generate what appears to be multiple mutations from a single recombinational intermediate. The resulting sequence divergence generates barriers to formation of viable recombinants. The multiple sequence changes can also lead to erroneous estimates in phylogenetic analyses.

Amino Acid Sequence↗

PubMed2001

Extreme morphological and ecological homoplasy in tropical salamanders.

Fossorial salamanders typically have elongate and attenuated heads and bodies, diminutive limbs, hands and feet, and extremely elongate tails. Batrachoseps from California, Lineatriton from eastern México, and Oedipina from southern México to Ecuador, all members of the family Plethodontidae, tribe Bolitoglossini, resemble one another in external morphology, which has evolved independently. Whereas Oedipina and Batrachoseps are elongate because there are more trunk vertebrae, a widespread homoplasy (parallelism) in salamanders, the genus Lineatriton is unique in having evolved convergently by an alternate "giraffe-neck" developmental program. Lineatriton has the same number of trunk vertebrae as related, nonelongated taxa, but individual trunk vertebrae are elongated. A robust phylogenetic hypothesis, based on sequences of three mtDNA genes, finds Lineatriton to be deeply nested within a clade characterized by generalized ecology and morphology. Lineatriton lineolus, the only currently recognized taxon in the genus, shows unanticipated genetic diversity. Surprisingly, geographically separated populations of L. lineolus are not monophyletic, but are sister taxa of different species of the morphologically generalized genus Pseudoeurycea. Lineatriton, long thought to be a unique monospecific lineage, is polyphyletic. Accordingly, the specialized morphology of Lineatriton displays homoplasy at two hierarchical levels: (i) with respect to other elongate lineages in the family (convergence), and (ii) within what is currently recognized as a single taxon (parallelism). These evolutionary events are of adaptive significance because to invade the lowland tropics salamanders must be either arboreal or fossorial; the repeated evolution of elongation and attenuation has led to multiple lowland invasions.

Animals↗