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Results for “Developmental programming”

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PubMed1995

Embryonic regulation of histone ubiquitination in the sea urchin.

We have used quantitative 2-D protein electrophoresis and immunoprecipitation to study the patterns of histone ubiquitination at 10 h and 36 h of embryonic development in Strongylocentrotus purpuratus. Variants csH2A, alpha H2A, beta H2A, gamma H2A, delta HA, H2AF./Z, alpha H2B, beta H2B, and gamma H2B showed up to sevenfold differences in level of monoubiquitination between variants, and individual variants showed up to sixfold changes during development. At 36 h of embryogenesis, the late variants were less ubiquitinated than the early variants, although the overall level of ubiquitination was appreciably greater than at 10 h. Antiubiquitin antibodies were used to precipitate formaldehyde-fixed chromatin fragments in order to estimate the degree of ubiquitination of the early histone genes. The 5' regulatory region of the active H3 gene appeared to be at least twice as ubiquitinated as the adjacent upstream spacer. However, the absolute level of ubiquitination of the early histone gene repeat seemed to be independent of transcriptional activity. These results show that variant-specific ubiquitination of histones is a part of the developmental program in sea urchin embryos, but is not clearly correlated with transcriptional activity of the early histone genes, except perhaps in the regulatory regions.

Animals↗

PubMed1997

Developmental regulation of Hsp32, a small heat shock protein in Dictyostelium discoideum.

We have examined the expression and heat inducibility of Hsp32, a novel small heat shock protein in Dictyostelium discoideum. Both Hsp32 and its mRNA are abundant in amoebae growing at physiological temperatures. Levels of Hsp32 remain high during the initial phases of development, including the formation of tipped mounds. After that stage, Hsp32 levels decrease, reaching barely detectable levels in culminating cells. In contrast, most of the hsp32 mRNA is rapidly degraded within the first few hours of starvation-induced development. Cells retain a new low steady state level of the mRNA throughout the rest of the developmental cycle. However, when cells undergo dedifferentiation, they reaccumulate high levels of hsp32 mRNA just prior to cell division. The heat inducibility of Hsp32 and its mRNA is maximal in growing cells and decreases as cells progress in their developmental program. The data suggest that Hsp32 is associated with a growth and/or survival function that is gradually eliminated during development.

Animals↗

PubMedDate not supplied

Effects of food shortage and oversupply on energy utilization, histology, and function of the gut in nestling song thrushes (Turdus philomelos).

We measured food intake, digestive efficiency, body mass increments, resting metabolic rate (RMR), carcass fat content, size and histological structure of the gut, and the rate of intestinal brush border uptake of l-proline in song thrush (Turdus philomelos) nestlings subjected to food shortage or food surplus under laboratory conditions. We assigned nestlings between 3 and 7 d of age to one of the following treatments: (1) food restriction, which resulted in a slowed growth at the rate found in undernourished, wild nestlings; (2) overfeeding, which totally suppressed begging; and (3) intermediate feeding. Threefold differences in energy consumption caused fivefold differences in body mass increments of the nestlings. Despite this, body mass-corrected RMR and intestinal mass were not affected by the feeding regime. The energy content of fecal output was highest in food-restricted birds, while their carcass fat content was lowest among treatment groups. Intestinal uptake rates of l-proline were low in the overfed and intermediate-fed young but significantly increased in the food-restricted birds, who attempted to maximize their rates of growth and development within the restrictive limits set by feeding regime. We noted a marked decrease of intestinal villi height in overfed birds as compared to intermediate-fed and food-restricted nestlings. We conclude that song thrush nestlings are characterized by a limited plasticity of their developmental program, which prohibits overfed nestlings from significantly up-regulating their gut function to accommodate increased food intake. This suggests that they already grew at a rate close to their physiological maximum. We suggest two interpretations: (1) under natural conditions, song thrush nestlings do not face frequent, unpredictable fluctuations in food abundance that could select for developmental plasticity, or (2) strong selection for uniform adult phenotypes prevents flexible developmental trajectories, which would result in a diversity of adult phenotypes.

Adipose Tissue↗

PubMed2004

The rice leaf blast pathogen undergoes developmental processes typical of root-infecting fungi.

Pathogens have evolved different strategies to overcome the various barriers that they encounter during infection of their hosts. The rice blast fungus Magnaporthe grisea causes one of the most damaging diseases of cultivated rice and has emerged as a paradigm system for investigation of foliar pathogenicity. This fungus undergoes a series of well-defined developmental steps during leaf infection, including the formation of elaborate penetration structures (appressoria). This process has been studied in great detail, and over thirty M. grisea genes that condition leaf infection have been identified. Here we show a new facet of the M. grisea life cycle: this fungus can undergo a different (and previously uncharacterized) set of programmed developmental events that are typical of root-infecting pathogens. We also show that root colonization can lead to systemic invasion and the development of classical disease symptoms on the aerial parts of the plant. Gene-for-gene type specific disease resistance that is effective against rice blast in leaves also operates in roots. These findings have significant implications for fungal development, epidemiology, plant breeding and disease control.

Amino Acid Sequence↗

PubMed1990

Lurcher Purkinje cells express glutamic acid decarboxylase and calbindin mRNAs.

Purkinje neurons in immature Lurcher (Lc/+) mice are destined to die as a result of a defect intrinsic to the dying cells. We have used in situ hybridization to determine whether the Lc allele interferes with the normal program of gene expression in the doomed Purkinje cells. In P21 mice, degeneration of Purkinje cells is well underway, but the surviving Purkinje cells continue to express the mRNAs for both glutamate decarboxylase and calbindin D28K, two proteins whose expression is characteristic of normal Purkinje neurons. We conclude that the Lc allele probably does not interfere with the developmental program but acts to cause cell death in already differentiated Purkinje neurons.

Alleles↗

PubMed2006

Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine.

The target of rapamycin (TOR) signaling pathway regulates cell growth and proliferation, however the extent to which TOR signaling mediates particular organogenesis programs remains to be determined. Here we report an examination of TOR signaling during zebrafish development, using a combination of small molecule treatment and morpholino-mediated gene knockdown. First, we amplified and sequenced the full-length cDNA for the zebrafish TOR ortholog (ztor). By in situ hybridization, we found that ztor is expressed ubiquitously in the early embryo, but displays a dynamic pattern in the gut between 48 and 72 h post-fertilization (hpf). Treatment of zebrafish embryos with rapamycin induced only a mild general developmental delay up to 72 hpf, but digestive tract development became arrested at the primitive gut tube stage. Rapamycin inhibited intestinal epithelial growth, morphogenesis and differentiation. Using morpholino-mediated gene knockdown of TOR pathway components, we show that this effect is mediated specifically by the rapamycin-sensitive TOR complex 1 (TORC1). Thus, in addition to regulating cell growth and proliferation, TOR signaling controls the developmental program guiding epithelial morphogenesis in the vertebrate intestine.

Animals↗

PubMed1998

Pax6 influences the time and site of origin of glial precursors in the ventral neural tube.

Neuroepithelial precursors in the ventral ventricular zone (VZ) of the spinal cord generate motor neurons (MNs) and interneurons, and then a subset of precursors starts to produce oligodendrocyte progenitors (OLPs). We show that OLPs originate in the ventral-most part of the Pax6-positive VZ, which at earlier times generates somatic (Isl2/Lim3-positive) MNs. In Small eye (Pax6-deficient) mice, the origin of OLPs is shifted dorsally and both OLPs and Isl2/Lim3 MNs are delayed. We suggest that somatic MNs and OLPs are generated sequentially from a common set of MN-OL precursors whose position in the VZ is influenced by Pax6. Neuron-glia fate switching might be a preprogrammed property of these precursors or a response to feedback from newly generated neurons. OLs developed normally in explants of Isl1(-/-) spinal cords, which lack MNs, arguing against feedback control and suggesting that the neuron-glia switch is an intrinsic developmental program in a specific subset of neural precursors.

Animals↗

PubMed2005

Phloem long-distance trafficking of GIBBERELLIC ACID-INSENSITIVE RNA regulates leaf development.

The phloem translocation stream contains a population of RNA molecules, suggesting plants use RNA to integrate developmental processes, at the whole-plant level. In the present study, we analyzed the role of long-distance trafficking in the delivery of transcripts from two members of the GRAS family, namely CmGAIP and GAI. These two homologs were chosen because of their involvement as transcriptional regulators in GA signaling. A combination of pumpkin, tomato and Arabidopsis was employed to examine the processes involved in long-distance delivery, to sink tissues, of RNA for engineered dominant gain-of-function pumpkin (Cmgaip) and Arabidopsis (DeltaDELLA-gai) genes. Our studies demonstrate that gai RNA entry into functional sieve elements occurs via a selective process. Both engineered mutant gai transcripts were able to exit the scion phloem and traffic cell to cell into the shoot apex. Delivery of Cmgaip and DeltaDELLA-gai RNA mediated highly reproducible changes in leaf phenotype in transgenic tomato lines grown under greenhouse conditions. Phenotypic analysis indicated that tomato leaflet morphology was influenced quite late in development. In addition, tissue sink strength did not appear to dictate gai RNA delivery, suggesting complexity in the process underlying macromolecular trafficking. These results establish that the molecular properties of the Cmgaip and DeltaDELLA-gai transcripts are compatible with the tomato cell-to-cell and long-distance macromolecular trafficking systems. An important conclusion, based on our work, is that control over GAI RNA delivery, via the phloem, may be regulated by sequence motifs conserved between plant families. We propose that RNA delivery via the phloem allows for flexibility in fine tuning of developmental programs to ensure newly developing leaves are optimized for performance under the prevailing environmental conditions.

Amino Acid Sequence↗

PubMed2005

Gene expression analysis by cDNA-AFLP highlights a set of new signaling networks and translational control during seed dormancy breaking in Nicotiana plumbaginifolia.

Seed dormancy in Nicotiana plumbaginifolia is characterized by an abscisic acid accumulation linked to a pronounced germination delay. Dormancy can be released by 1 year after-ripening treatment. Using a cDNA-amplified fragment length polymorphism (cDNA-AFLP) approach we compared the gene expression patterns of dormant and after-ripened seeds, air-dry or during one day imbibition and analyzed 15,000 cDNA fragments. Among them 1020 were found to be differentially regulated by dormancy. Of 412 sequenced cDNA fragments, 83 were assigned to a known function by search similarities to public databases. The functional categories of the identified dormancy maintenance and breaking responsive genes, give evidence that after-ripening turns in the air-dry seed to a new developmental program that modulates, at the RNA level, components of translational control, signaling networks, transcriptional control and regulated proteolysis.

Blotting, Northern↗

PubMed1994

Anti-apogens and anti-engulfens: monoclonal antibodies reveal specific antigens on apoptotic and engulfment cells during chicken embryonic development.

We have isolated a group of monoclonal antibodies that specifically recognize either apoptotic or engulfment cells in the interdigit areas of chicken hind limb foot plates, and throughout the embryo. Ten of these antibodies (anti-apogens) detect epitopes on dying cells that colocalize to areas of programmed cell death, characterized by the presence of apoptotic cells and bodies with typical cellular and nuclear morphology. Our results indicate that cells destined to die, or that are in the process of dying, express specific antigens that are not detectable in or on the surface of living cells. The detection of these apoptotic cell antigens in other areas of programmed cell death throughout the chick embryo indicates that different cell types, which form specific tissues and organs, may utilize similar cell death mechanisms. Six of the monoclonal antibodies (antiengulfens) define a class of engulfment cells which contain various numbers of apoptotic cells and/or apoptotic bodies in areas of programmed cell death. The immunostaining pattern of the anti-engulfen R15F is similar to that of an antibody against a common leukocyte antigen, suggesting the participation of cells from the immune system in the removal of apoptotic cell debris. These novel monoclonal antibody markers for apoptotic and engulfment cells will provide new tools to assist the further understanding of developmental programmed cell death in vertebrates.

Animals↗

PubMed1995

In vitro maturation of clonal CD4+CD8+ cell lines in response to TCR engagement.

Engagement of the TCR on immature CD4+CD8+ (DP) thymocytes by an appropriate peptide/MHC ligand evokes a complex program of maturation known as positive selection. As a result, DP thymocytes are rescued from programmed cell death, become committed to the CD4 or CD8 lineage, extinguish expression of V(D)J recombinase activity, and undergo further maturation. We describe here a panel of DP thymic lymphoma cell lines that, in response to in vitro TCR engagement, undergo many of the TCR-beta-induced maturation events that have been reported to accompany positive selection of DP thymocytes in vivo. These events include increased expression of CD5, CD69, CD45, TCR-alpha, and MHC class I, and decreased expression of Thy-1 and heat-stable Ag. In addition, we observed TCR-induced expression of the bcl-2 gene, a well described inhibitor of programmed cell death. Finally, TCR engagement decreased expression of recombinase-activating genes and terminal deoxynucleotidal transferase genes, as well as V(D)J recombinase activity. However, TCR engagement did not elicit demonstrable CD4/CD8 lineage commitment. These observations suggest that engagement of the TCR on these DP cell lines elicits multiple maturation events that are part of the positive selection developmental program, but not CD4/CD8 lineage commitment. Thus, these DP cell lines provide the opportunity to elucidate molecular mechanisms of maturation and CD4/CD8 lineage commitment in vitro.

Animals↗

PubMed1999

Evolutionary change in the functional specificity of genes.

Species throughout the animal kingdom share not only housekeeping but also many key regulatory genes. Nonetheless, species differ from one another developmentally and thus, also morphologically. One of the general aims of comparative developmental genetics is to understand how similar molecules can generate the known diversity of biological form. Here, we argue that gene function can change in different ways during the evolution of developmental processes. Genes can be recruited to serve completely new functions in a new regulatory linkage (co-option), they can change their molecular specificity while remaining in the original (homologous) developmental program and can, at the same time, retain other functions. We describe evidence for such evolutionary patterns based on the comparison of loss-of-function mutations of homologous genes of the two free-living nematodes Caenorhabditis elegans and Pristionchus pacificus. Ultimately, it is the interplay of conservation and change of the specificity of genes and genetic networks that generates developmental novelty over evolutionary time.

Animals↗

PubMed1982

Cyclic nucleotide-induced maturation of human promyelocytic leukemia cells.

Myeloid differentiation in vitro is characterized by the sequential appearance of morphological, functional, and biochemical markers of maturation. We examined the effect of agents that increased the intracellular concentration of adenosine 3'5'-cyclic monophosphate on the expression of these markers by human promyelocytic leukemia cells (HL60). Cells treated with 500 muM N(6),O(2)-dibutyryl adenosine 3'5'-cyclic monophosphate expressed formyl peptide and complement receptors, reduced nitroblue tetrazolium, adhered to substrate, demonstrated chemotaxis and stimulated lysosomal enzyme release, rapidly ceased proliferation, and assumed the morphology of myelocytes and metamyelocytes. Prostaglandin E(2) (100 nM) and theophyllin (500 muM) induced similar functional changes but the cells did not mature beyond the myelocyte stage. Cholera toxin (1 or 50 nM) induced formyl-peptide receptor expression and adherence, but the cells did not reduce nitroblue tetrazolium, continued to proliferate, and were unchanged morphologically. Formyl-peptide receptor expression was the earliest marker of these modified programs of maturation. The receptor appeared within 2 h after treatment and increased linearly for 72 h. Receptor expression was dependent on new protein synthesis. At 48 h, Scatchard analysis demonstrated 2.4 x 10(5) receptors/ cell with a K(D) of 1.3 nM. In contrast to induction of HL60 differentiation by dimethyl sulfoxide, retinoic acid, or phorbol myristate acetate, the developmental programs initiated by agents that raised intracellular adenosine 3'5'-cyclic monophosphate shared several unique features: (a) plasma membrane maturation was dissociated from morphological maturation; (b) no latent period was evident following induction-the earliest membrane marker was expressed within 2 h; (c) commitment to terminal differentiation was delayed.

Binding, Competitive↗

PubMed2000

Ectopic expression of luteinizing hormone-releasing hormone and peripherin in the respiratory epithelium of mice lacking transcription factor AP-2alpha.

The vertebrate transcription factor activator protein-2 (AP-2alpha) is involved in craniofacial morphogenesis. In the nasal placode AP-2alpha expression delineates presumptive respiratory epithelia from olfactory epithelia, with AP-2alpha expression restricted to the anterior region of the respiratory epithelium (absent from the olfactory epithelium) at later stages. To address the role AP-2alpha plays in differentiation of cell groups in the nasal placode, the spatiotemporal expression pattern of four markers normally associated with olfactory epithelial structures was analyzed in mice lacking AP-2alpha. These markers were the intermediate filament protein peripherin, the neuropeptide luteinizing hormone-releasing hormone (LHRH), the neural cell adhesion molecule (NCAM) and the olfactory transcription factor Olf-1. Development of cells expressing these markers was similar in both genotypes until embryonic day 12.5 (E12.5), indicating that the main olfactory epithelium and olfactory pit formation was normal. At E13.5 in mutant mice, ectopic LHRH neurons and peripherin axons were detected in respiratory epithelial areas, areas devoid of Olf-1 and NCAM staining. Over the next few days, an increase in total nasal LHRH neurons occurred. The increase in nasal LHRH neurons could be accounted for by LHRH neurons arising and migrating out of respiratory epithelial regions on peripherin-positive fibers. These results indicate that AP-2alpha is not essential for the separation of the olfactory and respiratory epithelium from the nasal placode and is consistent with AP-2alpha preventing recapitulation of developmental programs within the respiratory epithelium that lead to expression of LHRH and peripherin phenotypes.

Animals↗

PubMed2026

Single-cell profiling decodes patagium development in gliding mammal.

The gliding patagium represents a key adaptation for mammalian flight, but its cellular development remains unexplored. Using single-nucleus RNA sequencing of embryonic flying squirrel patagium and dorsal skin, we construct a single-cell atlas of patagium development and identify two distinct fibroblast subpopulations (Fp2 and Fr) highly enriched in the patagium. These fibroblasts are characterized by the patagium upregulation of Wnt5a, Fgf7, and Fgf10, and are associated with patagium morphogenesis through dermal-epidermal putative communication interactions between dermal fibroblasts (Fp2 and Fr) and epithelial basal keratinocytes. Specifically, Fp2 fibroblasts are potentially involved in distal dermal condensation and epithelial thickening together with elevated Wnt5a expression, while both Fp2 and Fr fibroblasts could play a role in epithelial polarization and thickening through Fgf7 and Fgf10, as suggested by ex vivo assays. Our data suggest that gliding patagium development results from the co-option of conserved WNT and FGF signaling pathways within a specialized fibroblast-epithelial context, illustrating how modifications of conserved developmental programs give rise to derived morphological traits.

Animals↗

PubMed1999

Differential expression of AP-2alpha and AP-2beta in the developing chick retina: repression of R-FABP promoter activity by AP-2.

Retinal fatty acid binding protein (R-FABP) is the avian counterpart of murine brain FABP implicated in glial cell differentiation and neuronal cell migration. R-FABP is highly expressed in the undifferentiated retina and brain of chick embryos. We have previously shown by in vitro studies that the AP-2 transcription factor binds to a consensus AP-2 binding site in the R-FABP promoter region. Based on the expression pattern of AP-2 in the developing retina and on mutational analysis of the AP-2 binding site in DNA transfection experiments, we proposed that AP-2 could be involved in the down-regulation of R-FABP transcription. Here, we describe the cDNA isolation of two members of the AP-2 family expressed in the chick retina, AP-2alpha and AP-2beta. We show that R-FABP mRNA and the AP-2 factors are expressed in mutually exclusive patterns in the differentiating retina: whereas AP-2alpha and AP-2beta are selectively expressed either in amacrine, or in amacrine and horizontal cells, respectively, R-FABP mRNAis found in Muller glial cells and/or bipolar cells. Furthermore, a decrease in R-FABP-dependent expression is obtained upon cotransfection of primary retinal cultures with AP-2 expression vectors and a CAT reporter construct. The early and cell-specific expression of AP-2alpha and AP-2beta in the developing retina suggest a role for this transcription factor family in the early steps of amacrine and horizontal cell differentiation. Repression of the R-FABP gene in these cells may be an important component of their developmental program.

Amino Acid Sequence↗

PubMed1991

Ultrastructure of dermal fibroblasts during development and aging: relationship to in vitro senescence of dermal fibroblasts.

One approach to understanding the relationship between in vitro cellular senescence and in vivo aging is to define the development and aging of cells in vivo and then to compare these in vivo properties with the in vitro behavior of the same cells. The Syrian hamster is being used as an experimental aging model to investigate the intrinsic developmental program of dermal fibroblasts in vivo (proliferation, extracellular matrix (ECM) production, quiescence, and reactivation during wound repair) in order to determine whether the in vivo differentiation program and mature function of these cells is related to their in vitro proliferation and senescence pattern. The ultrastructure of dermal fibroblasts from midfetal development through old age is described, and a working hypothesis of the development and aging of dermal fibroblasts is proposed as a framework for further evaluation of the relationship between in vitro proliferative capacity of dermal fibroblasts and in vivo developmental and age-related changes in the dermis.

Aging↗

PubMed2004

Developmental regulation of expression of renal potassium secretory channels.

PURPOSE OF REVIEW: Somatic growth is associated with an increase in total body K content. K homeostasis is regulated, in large part, by urinary K excretion. Within the adult kidney and specifically the cortical collecting duct, K secretion is accomplished by the passive diffusion of cell K into the urinary fluid down a favorable electrochemical gradient through K selective channels. The purpose of this review is to summarize the results of recent studies that provide insight into how the cortical collecting duct is uniquely adapted for K retention early in life. RECENT FINDINGS: Electrophysiological analyses have identified two types of apical K channels in the mammalian cortical collecting duct. The prevalence of the secretory K channel and its high open probability at the resting membrane potential in the adult has led to the belief that this channel mediates baseline K secretion. The Ca and stretch-activated maxi-K channel has been proposed to mediate flow-stimulated K secretion. In contrast to the high rates of K secretion observed in adult cortical collecting ducts microperfused in vitro, segments isolated from neonatal animals show no significant net K transport until after the third week of postnatal life. The temporal delay between expression of conducting secretory K channels (baseline K secretion) and maxi-K channels (flow-stimulated K secretion) in the maturing cortical collecting duct reflect unique developmental programs regulating the transcription and/or translation of ROMK (rat outer medullary K channel) and slo, the molecular correlates of the secretory K and maxi-K channels, respectively. SUMMARY: The K retention characteristic of the neonatal kidney is due, in part, to a paucity of distinct K channels mediating baseline and flow-stimulated K secretion in the collecting duct. The signals directing the developmental regulation of channel expression are as yet unknown.

Age Factors↗