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Results for “Developmental programming”

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PubMed1975

Determination of air movement in stored grain as a factor in dynamic dispersion and distribution patterns of gaseous pesticides (fumigants).

The new research reported herein was motivated by variations in distribution-persistence patterns of fumigant residues (BERCK, 1974). The current developmental program is still underway. In the meantime, measurement of picoliter amounts of SF6 in air by GC equipped with a Ni63 EC detector has been proven useful over an airflow range of 10(-4) to 50 mph, representing a factor of 500,000 in differences in air velocity. Diverse applications have been outlined herein. This is the first case on record where measurement of unassisted airflow in the interstitial air of stored grain has been successfully executed, and which enabled determination of airflow speeds in the range of 0.5 to 7.5 times 10(-4) mph (=3 to 45 inches per hour).

Air Movements↗

PubMed1990

Regulation of galactose metabolism: implications for therapy.

In view of evidence that dietary therapy of galactose-1-phosphate uridyltransferase deficiency has failed to prevent complications of the disorder, there is a need for new strategies in treatment. The enhancement of residual enzyme activity in tissues of galactosaemic patients should provide such an approach. This possibility is derived from knowledge of the regulation of transferase activity in normal animal tissues. The pertinent observations summarized herein are: (1) that hepatic transferase activity is modulated by various cellular metabolites, uridine nucleotides being of particular significance; (2) that transferase activity in the young rat liver is subject to developmental programming with a several-fold increase after birth; (3) that transferase activity in pregnant rat liver is significantly increased which may be related to hormonal effects of progesterone; and (4) that pharmacological doses of folic acid may increase transferase activity. The basis of such regulation can give insight into sufficient augmentation of the residual activity to increase galactose utilization and thereby better the long-term outcome.

Animals↗

PubMed1981

Modulation of differentiation in vitro. I. Influence of the attachment surface on myogenesis.

Myogenic cells of the L6 line proliferate and fuse in culture to form myotubes that actively synthesize muscle-specific proteins such as myosin. We show that the expression of the differentiated phenotype can be influenced by the electrical charges of the substratum on which the cells were grown. Negatively charged surfaces did not influence the developmental program of the cells although positively charged ones interfered with myogenesis. The interaction operates primarily by interfering with the mitotic cycle, which is slowed down, with fusion which is blocked, and with myosin synthesis, which is reduced. Our results show that growth of the cells on positively charged surfaces prevents the switching of a large fraction of the population from a proliferative state to a differentiating program. We postulate that this interference might operate through the slowdown in DNA replication. The cell culture method described represents a good model for studying the different steps involved in the differentiation of L6 cells.

Animals↗

PubMed1989

A simple, disposable, and improved organ culture system for maintaining three-dimensional development of mouse embryonic molars.

Mandibular first molars from 17-d-old mouse embryos were cultured in vitro for 2 to 4 d by a simple, disposable, improved floatation method. This method consisted of using a 24-well multidish and a plastic culture chamber with a membrane filter. The improved floatation method, as well as our previous method, was capable of the three-dimensional development of tooth germs. Cytodifferentiation of odontoblasts and ameloblasts and formation of extracellular matrices were accelerated by the present culture system, in comparison with our previous method. All the molars cultivated by this method were very similar in morphology to in vivo. On Day 2 of culture the terminal cytodifferentiation of odontoblasts and the formation of predentin were ascertained in the bucco-lingual sections of the cultured molars. A thick layer of predentin was formed at the tip of the cusp and gradually decreased toward the cervical loop and the fissure between the buccal and lingual cusps. On Day 4 in vitro, secretory ameloblasts produced enamel matrix, and the mineralized enamel showed showed prismatic structure very similar to that in vivo. Dentin and predentin also were normal in ultrastructure. The extracellular matrices (enamel, dentine, and predentin) were formed in line with the pattern of the cusp and the formation of matrices normally started at the tip of the cusp. We conclude that the three-dimensional development of whole tooth germs in vitro may be very important for normal expression of the developmental program intrinsic to mouse embryonic molars.

Animals↗

PubMed1986

Cell differentiation and malignancy.

An understanding of the mechanism that controls growth and differentiation in normal cells would seem to be an essential requirement to elucidate the origin and reversibility of malignancy. For this approach I have mainly used normal and leukemic blood cells, and in most studies have used myeloid blood cells as a model system. Our development of systems for the in vitro cloning and clonal differentiation of normal blood cells made it possible to study the controls that regulate growth (multiplication) and differentiation of these normal cells and the changes in these controls in leukemia. Experiments with normal blood cell precursors have shown that normal cells require different proteins to induce growth and differentiation. We have also shown that in normal myeloid precursors, growth-inducing protein induces both growth and production of differentiation-inducing protein so this ensures the coupling between growth and differentiation that occurs in normal development. The origin of malignancy involves uncoupling of growth and differentiation. This can be produced by changes from inducible to constitutive expression of specific genes that result in asynchrony to the coordination required for the normal developmental program. Normal myeloid precursors require an external source of growth-inducing protein for growth, and we have identified different types of leukemic cells. Some no longer require and other constitutively produce their own growth-inducing protein. But addition of the normal differentiation-inducing protein to these malignant cells still induces their normal differentiation, and the mature cells are then no longer malignant. Genetic changes that produce blocks in the ability to be induced to differentiate by the normal inducer occur in the evolution of leukemia. But even these cells can be induced to differentiate by other compounds, including low doses of compounds now being used in cancer therapy, that induce the differentiation program by other pathways. This differentiation of leukemic cells has been obtained in vitro and in vivo, and our in vivo results indicate that this may be a useful approach to therapy. In some tumours, such as sarcomas, reversion from a malignant to a non-malignant phenotype can be a result of chromosome changes that suppress malignancy. But in myeloid leukemia, the stopping of growth in mature cells by induction of differentiation bypasses the genetic changes that produce the malignant phenotype. These conclusions can also be applied to other types of normal and malignant cells.

Animals↗

PubMed2002

Transcriptional regulation of myelopoiesis.

A common myeloid progenitor gives rise to both granulocytes and monocytes. The early stages of granulopoiesis are mediated by the C/EBPalpha, PU.1, RAR, CBF, and c-Myb transcription factors, and the later stages require C/EBPepsilon, PU.1, and CDP. Monocyte development requires PU.1 and interferon consensus sequence binding protein and can be induced by Maf-B, c-Jun, or Egr-1. Cytokine receptor signals modulate transcription factor activities but do not determine cell fates. Several mechanisms orchestrate the myeloid developmental program, including cooperative gene regulation, protein:protein interactions, regulation of factor levels, and induction of cell cycle arrest.

Animals↗

PubMed2004

Environmentally induced long-term structural changes: cues for functional orientation and vulnerabilities.

Environmental challenges profoundly modify phenotypes and disrupt inherent developmental programs both at functional and structural levels. As an example, we have studied the impact of these environmental influences on adult neurogenesis in the dentate gyrus. Neurogenesis results from an inherent program, participates to hippocampal network organization and, as a consequence, to the various functional abilities depending on this region, including memories. In preclinical studies of aging we have shown that phenotypes vulnerable to the development of spatial memory disorders are characterized by lower hippocampal neurogenesis. We have hypothesized that these interindividual variations in functional expression of neurogenesis in senescent subjects could be predicted early in life. Indeed, a behavioral response (novelty-induced locomotor reactivity) and a biological trait (hypothalamo-pituitary-adrenal axis activity), which are predictive of cognitive impairments later in life, are related to neurogenesis in young adult rats. This suggests that subjects starting off with an impaired neurogenesis, here rats that are high reactive to stress, are predisposed for the development of age-related cognitive disorders. We have further shown that these inter-individual differences result from early deleterious life events. Indeed, prenatal stress orients neurogenesis in pathological ways for the entire life, and precipitates age-related cognitive impairments. Altogether these data suggest first that hippocampal neurogenesis plays a pivotal role in environmentally-induced vulnerability to the development of pathological aging, and second that environmental challenges and life events orient structural developments, leading to different phenotypes.

Animals↗

PubMed1997

Thalamic and cortical projections to middle suprasylvian cortex of cats: constancy and variation.

We investigated the constancy and variability in the numbers of thalamic and cortical neurons projecting to cat middle suprasylvian (MS) visual cortex. Retrograde pathway tracers were injected at a single anatomically and physiologically defined locus in MS cortex. Counts of labeled neurons showed that the visual thalamic projections to MS cortex consistently arose from a fixed set of nuclei in relatively constant proportions. In contrast, counts of cortical neurons revealed that transcortical inputs to MS cortex were much more variable. This differential variability may be linked to the developmental program, which affords greater influence of experiential factors on cortical pathway development than on thalamocortical pathway development. These results have implications for the development of models of cerebral connectivity that include measures of pathway variability.

Animals↗

PubMed1997

Immune-deficient SCID and NOD/SCID mice models as functional assays for studying normal and malignant human hematopoiesis.

Many events and requirements of the developmental program of human hematopoietic stem cells have not yet been discovered. A major impediment has been the lack of an appropriate experimental system. At present the conditions for maintaining human stem cells in vitro are not fully known. As a result within a short period the small stem cell pool is lost due to differentiation, making it difficult to examine the correlation between these cells and their function in vivo. Most of our knowledge of hematopoietic stem cells is from animal models in which purified stem cell canididates are assayed based on their functional ability to rescue lethally conditioned recipients. The permanent correction of many genetic disorders of the hematopoietic system requires efficient methods for introducing genes into stem cells in vitro. However, progress has been hindered by the absence of preclinical models that assay the repopulating capacity of primitive human cells. In addition, the development of therapy for malignant diseases also requires assays to identify the target leukemic stem cells based on their ability to initiate the disease. The recent development of methods to transplant or implant both normal and leukemic cells into immune-deficient mice provides the foundation for human stem cell assays. These models assay the repopulating capacity of primitive human cells and provide an important approach to identify and characterize human stem cells, both normal and leukemic. This review focuses on the development of functional assays for normal and leukemic human stem cells and on the new insights that these models are beginning to provide on the organization of the human stem cell hierarchy.

Animals↗

PubMed1997

[Specification of cell destiny in early Caenorhabditis elegans embryo].

Embryogenesis of the nematode Caenorhabditis elegans has been described completely on a cell-by-cell basis and found to be essentially invariant. With this knowledge in hands, micromanipulated embryos and mutants have been analyzed for cell lineage defects and the distribution of specific gene products. The results challenge the classical view of cell-autonomous development in nematodes and indicate that the early embryo of C. elegans is a highly dynamic system. A network of inductive events between neighboring cells is being revealed, which is necessary to assign different developmental programs to blastomeres. In those cases where molecules involved in these cell-cell interactions have been identified, homologies to cell surface receptors, ligands and transcription factors found in other systems have become obvious.

Animals↗

PubMed2002

Morphological and physiological changes in Streptomyces lividans induced by different yeasts.

Streptomyces development is a complex process that eventually finishes with the formation of individual unigenomic spores from the aerial hyphae. Intraspecific and interspecific signals must play a key role in triggering or blocking this process. Here we show that interaction between two types of microorganisms, Streptomyces and yeasts, leads to alteration of the Streptomyces developmental program. This alteration is due to the action of invertase produced by the yeast on the sucrose present in the culture media, making glucose and fructose readily available for growth.

Culture Media↗

PubMed2000

Postnatal development of differential projections from the caudal and rostral motor cortex subregions.

The primary motor cortex of cats, monkeys, and humans has distinct rostral and caudal subregions. In the cat, projections from the caudal subregion terminate predominantly in laminae 4-6 and, from the rostral subregion, in laminae 6-8. The purpose of this study was to determine if these distinctive termination patterns are present during early postnatal development, when corticospinal axons are establishing connections with spinal neurons, or if there was postnatal refinement of the distribution of terminations. We used the anterograde tracer biotinylated dextran amine (BDA) to label selectively projections from the two subregions in immature (postnatal days 25, 35 at time of analysis) and mature animals. We compared the distribution of spinal gray matter labeling from caudal and rostral motor cortex. In immature animals, substantial bilateral terminations were present after tracer injection into either subregion. Partial axon reconstructions revealed that individual axons terminated bilaterally. The dorso-ventral laminar distribution of contralateral labeling after caudal motor cortex injections was significantly more extensive for immature than mature animals. In immature animals, most of the labeling was present in laminae 5-7 (dorsal portion). with lesser amounts in laminae 1-4 and 7 (ventral portion), 8, and 9. In mature animals, there were significant reductions in the amount of label in laminae 7-9, resulting in contraction of the labeled territory. The distribution of dorsal horn-ventral horn labeling shifted from 41% and 59% in immature animals to 77% and 23% in maturity. The distribution of contralateral labeling after rostral motor cortex injections also was different in immature and mature animals, but the changes were less extensive than for the caudal motor cortex. In immature animals, the distribution of labeling was similar to that after caudal motor cortex injections in animals of the same age. In mature animals, there was a significant reduction in the amount of labeling in laminae 1-4 and a smaller reduction in 7 (ventral)-9. The overall dorsal horn-ventral horn distribution, however, remained largely unchanged, from 40% and 60% in immature animals to 44% and 56% in maturity. In immature animals after rostral motor cortex injection, corticospinal terminations were present within the lateral motor nuclei. Thus, the distinctive spinal termination patterns of caudal and rostral motor cortex in maturity each reflected postnatal refinement of the distribution of axon terminations. It is plausible that the dorso-ventral refinement of corticospinal terminations relies on activity-dependent competition between caudal and rostral motor cortex, similar to activity-dependent refinement of the laterality of terminations. Our results, however, suggest that the developmental program for achieving corticospinal connectional specificity by the two subregions is different because there was large-scale refinement of the terminations of caudal motor cortex but only local refinement of rostral motor cortex terminations.

Age Factors↗

PubMed1999

The molecular genetics of holoprosencephaly: a model of brain development for the next century.

The recent identification of some of the human holoprosencephaly genes is beginning to elucidate the intricate developmental programs that pattern normal and abnormal brain development. Here we present some of these advances in the context of our present understanding and conclude with some speculations regarding the direction for future investigations. We are living in a tremendously exciting time in medicine with the rapid application of molecular genetic approaches to the understanding of human disease. It is the purpose of this review to stress the underlying principals of our approach at a level that can be readily appreciated by colleagues who themselves are experts in brain anatomy but not necessarily the molecular genetics of brain development.

Central Nervous System↗

PubMed2001

Immunolocalization of FAS and FAS ligand in inflammatory myopathies.

Fas/Fas ligand (FasL) interaction can induce apoptosis, have a costimulatory role or act as a mechanism by which cytotoxic T cells produce target cell lysis. We used several commercially available antibodies to study Fas and FasL expression in polymyositis (PM), inclusion body myositis (IBM), dermatomyositis (DM) and normal controls. A strong Fas signal occurred on the sarcolemma, and to a lesser extent in the sarcoplasm of neural cell adhesion molecule (NCAM)-positive or developmental myosin heavy chain-positive regenerating muscle fibers and of injured fibers with presumed abortive regenerative activity, including some nonnecrotic invaded fibers in PM and IBM and some of the atrophic perifascicular fibers in DM. Most fibers within groups of atrophic fibers in IBM were strongly Fas-positive, and statistically more muscle fibers were Fas-positive in IBM compared to PM. A subset of the actively invading CD8+ T cells in nonnecrotic muscle fibers in PM and IBM, and scattered CD4+ cells in each inflammatory myopathy, had up-regulated Fas expression, probably reflecting costimulation. No FasL antibody consistently labeled the positive control tissue (testis) or intramuscular elements in control or inflammatory myopathy specimens. Our study identifies regenerating muscle fibers as the main site of Fas immunoreactivity in inflammatory myopathies, and Fas expression may be part of an activated or reactivated developmental program of new gene expression in regenerating or denervated muscle fibers. Our data plead against a specific role of Fas/FasL interaction in the immunopathogenesis of the inflammatory myopathies.

CD8 Antigens↗

PubMed1997

Ubiquitination of apoptotic cells in the developing cerebellum of the rat following ionizing radiation or methylazoxymethanol injection.

Previous studies have shown ubiquitin mRNA induction and protein expression associated with regressive phenomena in some cases of developmentally programmed cell death and experimentally induced apoptosis. Ubiquitin immunoreactivity was examined in the developing cerebellum of the rat following ionizing radiation or methylazoxymethanol (MAM) injection. In irradiated rats, apoptotic cells in the external granule cell layer appeared at 3 h, peaked at 6 h, and decreased thereafter to reach nearly normal values at 48 h. In MAM-treated rats, apoptotic cells in the external granule cell layer were seen at 24 h, peaked at 48 h, and decreased at 72 h. Strong ubiquitin expression was observed in about 15% of apoptotic cells at later stages of apoptosis in both experimental models of induced cell death. In irradiated rats, strong ubiquitin immunoreactivity in apoptotic cells and cellular debris was observed 12 h after irradiation, peaking at 24 h, and decreasing at 48 h. In MAM-treated rats, strong ubiquitin immunoreactivity was found in apoptotic cells and cellular debris at 48 h and decreased at 72 h. Results suggest that activation of the ubiquitin pathway is not a signal that triggers apoptosis but rather a final step in the apoptotic process.

Alkylating Agents↗

PubMed2001

Somatic embryogenesis from Arabidopsis shoot apical meristem mutants.

Zygotic embryos of three Arabidopsis thaliana (L.) Heynh. mutants lacking an embryonic shoot apical meristem (SAM), shoot meristemless (stm), wuschel (wus) and zwille/pinhead (zll/pnh) were used as explants to establish embryogenic cell cultures. Somatic embryos of all three mutants showed the same mutant phenotypes as their zygotic equivalents. These results provide genetic evidence that the developmental program of somatic and zygotic embryos is indistinguishable. They also suggest that a functional SAM is not required for somatic embryogenic cell formation in Arabidopsis.

Arabidopsis↗

PubMed2002

Insights into the G1/S transition in plants.

The G1/S transition generally represents the principal point of commitment to cell division. Many of the components of the cell cycle core machinery regulating the G1/S transition in plants have been recently identified. Although plant regulators of the G1/S transition display structural and biochemical homologies with their animal counterparts, their functions in integrating environmental stimuli and the developmental program within cell cycle progression are often plant-specific. In this review, recent progress in understanding the role of plant G1/S transition regulators is presented. Emerging evidence concerning the mechanisms of G1/S control in response to factors triggering the cell cycle and the integration of these mechanisms with plant development is also discussed.

Cell Cycle↗

PubMed2003

Apical meristem organization and lack of establishment of the quiescent center in Cactaceae roots with determinate growth.

Some species of Cactaceae from the Sonoran Desert are characterized by a determinate growth pattern of the primary root, which is important for rapid lateral-root formation and seedling establishment. An analysis of the determinate root growth can be helpful for understanding the mechanism of meristem maintenance in plants in general. Stenocereus gummosus (Engelm.) Gibson & Horak and Pachycereus pringlei (S. Watson) Britton & Rose are characterized by an open type of root apical meristem. Immunohistochemical analysis of 5-bromo-2'-deoxyuridine incorporation into S. gummosus showed that the percentage of cells passing through the S-phase in a 24-h period is the same within the zone where a population of relatively slowly proliferating cells could be established and above this zone in the meristem. This indicated the absence of the quiescent center (QC) in S. gummosus. During the second and the third days of growth, in the distal meristem portion of P. pringlei roots, a compact group of cells that had a cell cycle longer than in the proximal meristem was found, indicating the presence of the QC. However, later in development, the QC could not be detected in this species. These data suggest that during post-germination the absence of the establishment of the QC within the apical meristem and limited proliferative activity of initial cells are the main components of a determinate developmental program and that establishment of the QC is required for maintenance of the meristem and indeterminate root growth in plants.

Cactaceae↗