PubMed Health⌕ Search

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 955 records · Page 53Linked to original sources
PubMed1993

Macrophages are required for cell death and tissue remodeling in the developing mouse eye.

To identify and characterize tissue remodeling processes mediated by macrophages, we have generated transgenic mice in which diphtheria toxin is expressed from a macrophage-specific transgene. Expression of the transgene disrupts subsets of mature macrophages in both the eye and the peritoneal cavity and results in the persistence of two normally transient ocular tissues, the hyaloid vasculature and the pupillary membrane. Furthermore, the cells comprising the pupillary membrane appear alive up to 14 days after the structure is normally remodeled, suggesting that the macrophage actively elicits target cell death. Thus, these transgenic mice provide direct evidence for the active involvement of macrophages in developmentally programmed tissue remodeling and identify the hyaloid vessels and the pupillary membrane in the eye as targets of macrophage-mediated remodeling.

Aging↗
PubMed1986

The stem cell concept revisited: self-renewal capacity is a dynamic property of hemopoietic cells.

A rigid developmental program of stem cell division and progressive maturation into blood cells is challenged. It is proposed that the capacity for self-renewal is not limited to pluripotent stem cells but is shared by committed progenitors and even cells of later compartments. The relative probability of self-replication vs maturation in mitotic cells is controlled by extracellular influences. At the cell population level, the balance between proliferation and maturation and between compartments is regulated by feedback interactions. Inducibility of maturation in response to regulatory signals is smaller at earlier stages; consequently, at steady state primitive cells self-renew while their more differentiated progeny are forced to be transitory. The proposed dynamic linkage between compartments can be destabilized in a number of ways, resulting in defective hemopoiesis or leukemia. At all stages hemopoietic cells are able to change their patterns of gene expression, in an inheritable manner, in response to changes in their microenvironment. In particular, the capacity for self-renewal itself can vary even within a conventionally-defined compartment. On this basis of adaptive differentiation and self-renewal it is possible to account for the progression of chronic myelocytic leukemia and its "blastic conversion"; to analyse the hemopoietic system's response to various physiological and experimental perturbations; and to re-interpret the excessive phenotypic plasticity and apparent "lineage infidelity" manifested by leukemic cells and cell lines.

Animals↗
PubMed1992

In vitro differentiation of trout oligodendrocytes: evidence for an A2B5-positive origin.

The molecular differentiation of oligodendrocytes derived from larval trout brain was studied in dissociated cell cultures using a range of cell type and stage specific antibodies. By double-labeling immunostaining using A2B5 antibodies in conjunction with antibodies against the myelin glycoproteins IP1 and IP2 evidence was obtained that oligodendrocytes of trout in vitro originate from A2B5+ precursor cells, which in terms of morphology closely resemble 0-2A progenitors of the mammalian CNS. Most surprisingly these cells did not differentiate in vitro beyond the level of IP2 expression, which signifies the initial step of oligodendroglial development in vivo. Hence it appears that in trout oligodendrocytes the initiation of the developmental program is intrinsically regulated, whereas further maturation of the cells requires appropriate environmental stimulation.

Animals↗
PubMed1993

Effect of insulin on GABAergic development in the embryonic chick retina.

We investigated the role of insulin in GABAergic differentiation in the embryonic chick retina at different embryonic ages using glutamate decarboxylase (GAD) and high-affinity GABA uptake as developmental markers. Both these GABAergic markers exhibit developmentally programmed increases in activity during retinogenesis that also occur in culture. Insulin stimulated GABA uptake in retina neurons at all embryonic ages in a dose-dependent manner and GAD activity by 30% in embryonic retina neurons after 11 days of development. The stimulation of GABA uptake by insulin was blocked by addition of ouabain suggesting a role for the Na+,K+ ATPase. The same concentration of insulin caused a 76% stimulation of protein synthesis in these retinal cells, and previous work demonstrated that insulin also stimulates cholinergic differentiation in the chick retina (Hausman et al., Dev. Brain. Res. 59, (1991) 31-37). Thus, there was no selective stimulation of GABAergic differentiation by insulin but likely a neurotrophic effect. The increase in GAD activity in neurons from post-11-day embryonic neurons contrasts with our previous findings at embryonic days 6-7 where there is little change in GAD activity after addition of insulin. It is possible that the failure of insulin to stimulate GAD activity during early retina development is due to the increased accumulation of GABA in the presence of insulin. GABA levels were increased more than two-fold by 100 ng/ml insulin.

Animals↗
PubMed1994

Morphological specification of trigeminal neurites depends on target fields.

Primary sensory neurons bridge the sensory periphery to the central nervous system (CNS) via their two axonal processes. The morphological patterning of the terminals of each process in its respective target is unique. Whether the differences between peripheral and central axons result from an intrinsic developmental program of the ganglion cell body, or from target-derived signals is not known. To explore this issue, we have used an explant coculture system in which embryonic (E15) trigeminal ganglion explants were placed between a vibrissa pad and a brainstem explant, but the explants were rotated 180 degrees relative to their normal orientation. In other experiments, individual ganglia were placed between two vibrissa pad explants or between two slices taken through the brainstem. The cultures were fixed after several days and ganglion cell processes were labeled with the lipophilic tracer DiI. Results of the ganglion rotation experiments suggest that trigeminal axons which would be directed centrally in vivo can regenerate into peripheral targets, and peripheral axons can grow into CNS tissue. Similarly, in cocultures with two peripheral or two central targets, both processes of trigeminal ganglion cells can simultaneously invade vibrissa pad explants or project into brainstem slices. Moreover, in all cocultures the differentiation of each set of processes is specific to the target innervated by it. These results show that the axons of embryonic sensory neurons are not selective in their choice of targets, and that their morphological patterning is dictated by target-derived signals.

Animals↗
PubMed1992

Target influences on the development of leech neurons.

A pair of Retzius neurons is found in each segmental midbody ganglion of the CNS of the leech Hirudo medicinalis. Although all Retzius neurons appear to have the same cell lineage and are indistinguishable from one another through the initial phases of axonogenesis, later in development two pairs of Retzius neurons--those in the segments containing the male and female reproductive ducts--acquire distinctive morphological and physiological characteristics. Experimental manipulations of the reproductive ducts in early embryos have indicated that the outgrowing Retzius axons receive a signal from these peripheral targets that triggers major changes in their developmental program. Such 'end-organ specification' has been shown to contribute to the differentiation of neurons in other nervous systems as well, and the mechanisms underlying such control can be investigated in great detail in the relatively simple, segmented nervous system of the leech.

Animals↗
PubMed1991

Characterization of a novel developmentally regulated gene from Trypanosoma brucei encoding a potential phosphoprotein.

We have isolated a cDNA clone corresponding to a single-copy nuclear gene that is upregulated at the mRNA level during in vitro differentiation of bloodstream trypomastigotes of strains of both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense to procyclic forms. Transcript levels begin to increase within minutes of introduction of bloodstream forms into culture and peak well before cultures exhibit a procyclic morphology. This increase in transcript levels was found to occur both in the absence of protein synthesis and in a nontransforming strain blocked very early in the developmental program, both conditions under which accumulation of procyclic acidic repetitive protein (PARP) transcripts did not occur in control experiments. DNA sequence analysis reveals an open reading frame sufficient to encode a protein of approximately 50 kDa within the cDNA, but data base searches for homology at either the amino acid or nucleotide level revealed no related sequences. A high density of kinase consensus target sites in the deduced amino acid sequence suggests that the gene product may be a phosphoprotein.

Amino Acid Sequence↗
PubMed1990

Selective activation of testis-specific genes in cultured rat spermatogenic cells.

During mammalian spermatogenesis the isozyme pattern of a glycolytic enzyme, phosphoglycerate kinase (PGK; ATP: 3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), changes from the somatic-type PGK-1 to the testis-specific PGK-2, and this change has been suggested to involve transcription switch. We have isolated genomic DNA fragments which code for the mouse PGK isozymes and determined the transcription start site of each gene. The results demonstrate that transcriptions of the two PGK genes are initiated at multiple sites under the control of TATA box-lacking promoters. The putative promoter regions of the two genes contain several distinct sequences known as the CCAAT box and the GC box which possibly bind CCAAT-binding proteins and Sp1, respectively. We next developed a culture system in which spermatogenic gene expression is partly reproduced. When spermatogenic cells of 20-day-old rats were cultured, transcripts from PGK-2 and another spermatogenic gene PRPS3 became detectable, while expression of other non-spermatogenic genes did not significantly change during culture. These results suggest that two spermatogenic genes PGK-2 and PRPS3 were activated in culture according to a developmental program of spermatogenesis. Thus, this culture system may be useful for studying the molecular mechanism underlying mammalian spermatogenic gene expression.

Animals↗
PubMed1995

A signaling pathway governing early thymocyte maturation.

Recent evidence supports the view that p56lck, a non-receptor protein tyrosine kinase, serves as the signaling element that 'senses' synthesis of a functional T-cell receptor beta chain, thereby promoting thymocyte maturation. Here, Steven Anderson and Roger Perlmutter review current data, and outline the features of this developmental program.

Animals↗
PubMed1989

Towards the molecular biology of cell adhesion in Drosophila.

The characterization of extracellular matrix molecules and their putative receptors is rapidly evolving in Drosophila. Where corresponding vertebrate and Drosophila extracellular proteins have been identified they are very similar with respect to their structural properties, suggesting a high degree of conservation during evolution. By contrast, indications for components homologous to vertebrate cell-cell adhesion molecules are still very sparse. Studies on the regulation of the Drosophila genes encoding cell adhesion molecules that are involved in general basic functions during morphogenesis, together with a knowledge of the function of the genes responsible for pattern formation, should lead towards a more complete understanding of the organism's developmental program.

Animals↗
PubMed1992

Chromatin diminution in nematode development.

Chromatin diminution in Parascaris and Ascaris represents the classical case of a developmentally programmed genome rearrangement. The process is very specific with respect to ontogenetic timing and chromosomal localization, and involves chromosomal breakage, new telomere formation and DNA degradation. Recent evidence from Ascaris lumbricoides var. suum suggests that chromatin diminution might have a function in gene regulation.

Animals↗
PubMed1995

Characterization of the 5' and promoter regions of the gene encoding the mouse neuronal cell adhesion molecule F3.

F3 is a 135 kDa neuronal cell surface adhesive glycoprotein belonging to the immunoglobulin supergene family (IgSF) which mediates heterophilic contact formation among neural cells and is involved in the control of neurite growth. F3 expression is regulated, during critical developmental periods, on neuronal subpopulations thus suggesting that control of F3 gene expression could be of morphogenetic relevance. To shed light on the mechanism involved in the control of F3 gene expression we isolated clones covering about 50 kilobases of the F3 gene which also included the promoter region. The study of F3 gene exon/intron organization revealed that, like other neural IgSF molecules, each of the first two F3 C2 domains is encoded by two exons while the N-terminus, the signal peptide and the 5' untranslated region are each encoded by distinct exons. A single transcription start site was identified, surrounded by a short 114 bp sequence able to direct reporter gene expression in both F3-expressing and -non-expressing cells. In addition, a cell type-specific enhancer, only active in F3-expressing cells, was found immediately upstream to it. Structural analysis of the promoter region revealed consensus sequences for binding transcription factors involved in cell type-specific and/or developmental regulations. Most of them are homeobox containing transcription factors thus suggesting that regulation of F3 gene expression could be part of a large developmental program.

Animals↗
PubMed1996

Dopamine transporter gene expression in rat mesencephalic dopaminergic neurons is increased by direct interaction with target striatal cells in vitro.

By using a semi-quantitative reverse transcriptase-PCR assay (RT-PCR) we have analyzed dopamine transporter (DAT), tyrosine hydroxylase (TH) and synaptic vesicle monoamine transporter (VMAT2) gene expression in rat mesencephalic (MES) primary cultures. Consistent with previous data obtained during rat MES ontogeny, the onset of DAT transcription in vitro is delayed in embryonic day (E)13, but not in E16, MES neurons when compared to that of TH and VMAT2. In co-culture, the addition of target striatal cells (STR) to E13 MES selectively increases DAT mRNA level in DA neurons during the first 3 days in vitro; cortical cells are ineffective. On the contrary, DAT gene does not appear up-regulated in E16 MES co-cultured with target STR cells, indicating that MES DA neurons respond to STR stimulation only at defined developmental stages. Up-regulation of DAT mRNA level by STR in E13 MES seems to require direct cell interactions since target cells do not exert their effect on DAT transcription when are separated from MES cells by a porous barrier, which only allows diffusion of soluble molecules. Thus maturation of DA neurotransmission in vitro appears to follow a developmental program which can be specifically modulated by their target STR cells.

Animals↗
PubMed1993

Quantum mechanical properties of biosystems: a framework for complexity, structural stability, and transformations.

Internal quantum non-demolition measurements are inherent for biological organization and determine the essential features of living systems. Low energy dissipation in these measurements provided by slow conformational relaxation of biomacromolecular complexes (regarded as measuring devices) is the main precondition of enzyme operation and information transfer determining the steady non-equilibrium state of biosystems. The presence of an internal formal description inside a biosystem, expressed in genetic structures (developmental program), is a consequence of its quantum properties. Incompleteness of this formal description provides the possibility of the generation of new functional relations and interconnections inside the system. This is a logical precondition of an evolutionary process. The quantum mechanical uncertainty that underlies the appearance of bifurcations is considered to be the main physical foundation of complication and irreversible transformation of biosystems.

Biological Evolution↗
PubMed1981

mRNA populations during wing development in the silkmoth Antheraea polyphemus.

Pupal wing tissue of the American silkmoth Antheraea polyphemus has been used as a model system to study 20-hydroxyecdysone and juvenile hormone control of cuticle protein synthesis. Juvenile hormone does not affect either the content or rate of synthesis of RNA and protein of the wing tissue. both of which show linear increases during the first few days of hormonal treatment. Based on the fractionation of total RNA on oligo-dT columns the percent of mRNA remains the same throughout development after both hormone treatments. However, both the amount of poly-A+ RNA in the wing tissue, and its content of poly-A show considerable increases as a function of development. The products of translation of the various poly-A+ RNA populations in the cell-free wheatgerm system have been analyzed by one- and two-dimensional gel electrophoresis and fluorography. Qualitative changes occur during the first 24 h; the production of a mRNA coding for a protein of approx. 40 000 dalton is stimulated and the production of a mRNA coding for a protein of 29 000 dalton is greatly reduced. Only a few differences are observed between samples from the 2 hormone treatments. Over the next 5-15 days of development mainly quantitative changes are observed. Juvenile hormone application results in quantitative changes in specific mRNAs, but no new mRNAs unique to juvenile hormone action are observed. The data are consistent with the concept that in altering the epidermal developmental program, juvenile hormone is apparently modulating the action of 20-hydroxyecdysone.

Animals↗
PubMed1992

Variations in cerebellar morphology of the Atlantic stingray, Dasyatis sabina.

The cerebellar corpus of the Atlantic stingray consists of an anterior lobe which is divided into rostral and caudal lobules, and a posterior lobe. The long axis of the posterior lobe and rostral lobule of the anterior lobe both lie along the midline, whereas the orientation of the caudal lobule varies. We examined this variation in 127 animals. In 52% the long axis of the caudal lobule lay on the right of the midline, in 21% it was on the left, and in 27% across the midline. While this distribution is not random, it is not related to size or sex. It is proposed that the observed variation is the reflection of variation in the cerebellar developmental program.

Animals↗
PubMed1993

Down-regulation of NMDA receptor activity by NMDA.

Rat cerebellar granule cells were cultured in a medium containing 25 mM KCl. The presence of NMDA during culture caused strong down-regulation of 45Ca uptake through the NMDA receptor channel. The process affected neither the viability nor the protein content of the cells. The developmental program of NMDA receptor activity was resumed after removal of NMDA from the culture medium, dependent apparently on protein synthesis. The down-regulation also rendered the neurons resistant to NMDA toxicity. It permitted replenishment of the culture with fresh medium, which is extremely toxic for cells cultured in absence of NMDA. Such down-regulation might perhaps play a role in adjusting the activity of post synaptic NMDA receptors, following synaptogenesis.

Animals↗