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Results for “Developmental programming”

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At least 451 records · Page 25Linked to original sources

PubMed1997

Proliferation, differentiation and morphogenesis of fetal rat glandular stomach transplanted under the kidney capsule of syngeneic hosts.

Undifferentiated glandular stomach tissue fragments from 16.5-day fetal rats were transplanted under the kidney capsule of syngeneic adult rats, and the proliferation, differentiation and morphogenesis of the transplanted tissues were investigated. Gastric epithelial cells began to invaginate 3-4 days after the transplantation and immature glands were formed after 1 week. During the period, there was a gradual increase in the expression of pepsinogen and cathepsin E, markers of cytodifferentiation of the stomach epithelia, both at protein and mRNA levels. Cathepsin E was weakly expressed in undifferentiated gastric epithelial cells at 16.5 days of gestation, and a higher level of the expression was observed in differentiated epithelia of the transplants. In contrast, the pepsinogen-producing cells first appeared around days 3-4 after transplantation and gradually increased in number to about 30% of the epithelial cells and became localized at the bottom of the gland. During the period of the experiment up to 1 month, the pepsinogen-producing cells were all positive for class III mucin and cathepsin E, indicating the immature character of these cells. In addition, no parietal cells were observed. When the tissue fragments were transplanted into adrenalectomized animals, the epithelial differentiation and morphogenesis was suppressed, but its proliferation was enhanced. The observed changes were reversed by hydrocortisone replacement. These results suggest that the development of the 16.5-day fetal stomach is regulated intrinsically to a certain extent by the genetic program of the cells involved and various gastric functions develop in the absence of luminal stimulation, stage-specific systemic hormonal change, neuronal regulation or other systemic influences, and that glucocorticoids modulate the developmental program of the fetal stomach tissues.

Adrenalectomy↗

PubMed2006

Signal transduction pathways leading to Ca2+ release in a vertebrate model system: lessons from Xenopus eggs.

At fertilization, eggs unite with sperm to initiate developmental programs that give rise to development of the embryo. Defining the molecular mechanism of this fundamental process at the beginning of life has been a key question in cell and developmental biology. In this review, we examine sperm-induced signal transduction events that lead to release of intracellular Ca(2+), a pivotal trigger of developmental activation, during fertilization in Xenopus laevis. Recent data demonstrate that metabolism of inositol 1,4,5-trisphosphate (IP(3)), a second messenger for Ca(2+) release, is carefully regulated and involves phospholipase C (PLC) and the tyrosine kinase Src. Roles of other potential regulators in this pathway, such as phosphatidylinositol 3-kinase, heterotrimeric GTP-binding protein, phospholipase D (PLD) and phosphatidic acid (PA) are also discussed. Finally, we address roles of egg lipid/membrane microdomains or 'rafts' as a platform for the sperm-egg membrane interaction and subsequent signaling events of egg activation.

Animals↗

PubMed2026

Spore type-specific gene expression profiles underlying development and leaf infection processes of Colletotrichum graminicola.

Colletotrichum graminicola causes significant losses of the staple crop maize worldwide. The fungus produces two distinct asexual spore types, oval and falcate conidia, which show unique processes in development and plant interaction. Based on genome resequencing of our laboratory strain (CgM2/M1.001), we investigated the gene expression profiles of oval and falcate conidia during development and early leaf infection using RNA-seq. Our results reveal specific gene expression profiles between the two spore types, indicating fundamental differences in their developmental programs that reflect different modes of infection. We identified expression patterns discriminating both conidia types from mycelium and spore type-specific ones for genes encoding transcription factors, conserved fungal developmental genes, transporters, genes of secondary metabolite clusters, and pathogenicity-related functions, including effectors and carbohydrate-active enzymes (CAZymes). Our study shows that despite the identical genomic basis, oval and falcate conidia show unique transcriptomes across vegetative development and early plant interaction. Taking together, these results provide new insights into the molecular mechanisms determining the biology of C. graminicola and its interaction with the plant host.

Colletotrichum graminicola↗

PubMed2003

Mechanisms of glucose signaling during germination of Arabidopsis.

Glucose (Glc) signaling, along with abscisic acid (ABA) signaling, has been implicated in regulating early plant development in Arabidopsis. It is generally believed that high levels of exogenous Glc cause ABA accumulation, which results in a delay of germination and an inhibition of seedling development-a typical stress response. To test this hypothesis and decipher the complex interactions that occur in the signaling pathways, we determined the effects of sugar and ABA on one developmental event, germination. We show that levels of exogenous Glc lower than previously cited could delay the rate of seed germination in wild-ecotype seeds. Remarkably, this effect could not be mimicked by an osmotic effect, and ABA was still involved. With higher concentrations of Glc, previously known Glc-insensitive mutants gin2 and abi4 exhibited germination kinetics similar to wild type, indicating that Glc-insensitive phenotypes are not the same for all developmental stages of growth and that the signaling properties of Glc vary with concentration. Higher concentrations of Glc were more potent in delaying seed germination. However, Glc-delayed seed germination was not caused by increased cellular ABA concentration, rather Glc appeared to slow down the decline of endogenous ABA. Except for the ABA-insensitive mutants, all tested genotypes appeared to have similar ABA perception during germination, where germination was correlated with the timing of ABA drop to a threshold level. In addition, Glc was found to modulate the transcription of genes involved in ABA biosynthesis and perception only after germination, suggesting a critical role of the developmental program in sugar sensing. On the basis of an extensive phenotypic, biochemical, and molecular analysis, we suggest that exogenous Glc application creates specific signals that vary with concentration and the developmental stage of the plant and that Glc-induced fluctuations in endogenous ABA level generate a different set of signals than those generated by external ABA application.

Abscisic Acid↗

PubMed1997

Prevention of normally occurring and deafferentation-induced neuronal death in chick brainstem auditory neurons by periodic blockade of AMPA/kainate receptors.

The role of glutamate receptors in regulating programmed neuronal death and deafferentation-induced neuronal death in the brainstem auditory nuclei was studied by in ovo drug administration to chick embryos. The nucleus laminaris (NL) undergoes programmed developmental cell death of 19% between embryonic day 9 (E9) and E17. The AMPA/kainate receptor antagonist CNQX, when administered at doses of 200-300 microg/d from E8 to E15, prevented programmed neuronal death in NL through at least posthatching day 8, without producing anatomical or behavioral abnormalities. 3-((RS)-2-Carboxypiperazin-4-yl)-propyl-1-phos-phonic acid, an antagonist of NMDA receptors, had no effect on normal cell death in the NL. CNQX, given from E8 to E15 or only from E8 to E10, also blocked the 33% neuronal loss in the nucleus magnocellularis (NM) that follows surgical destruction of the otocyst on E3, a procedure that deafferents NM neurons by preventing formation of the cochlear nerve. Treatment either with CNQX or the more highly selective NBQX from E8 to E10, before the onset of synaptic transmission in NM and NL, was also effective in preventing normal neuronal death in NL. Analysis of the effects of CNQX or NBQX on spontaneous embryonic motility at E10 showed that the doses effective in preventing neuronal death suppressed motility for <8 hr. We conclude that periodic blockade of AMPA/kainate receptors can protect CNS neurons against subsequent programmed cell death or deafferentation-induced death.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2002

Lamprey as an evo-devo model: lessons from comparative embryology and molecular phylogenetics.

Lamprey, the living jawless vertebrate, has been regarded as one of the most primitive groups of vertebrates. The evolutionary phylogenetic position of the lamprey promises to provide hints about the origin of the vertebrate genome as well as the origin of the body plan, a part of which may be written in the genome. Since the lamprey split from the gnathostome lineage early in the history of vertebrates, the shared developmental mechanisms in lampreys and gnathostomes can be regarded as possessed by the hypothetical common ancestor of these animals, whereas the gnathostome-specific developmental mechanisms that are absent from lampreys indicate that they are relatively new, added to the developmental program only after the split of gnathostomes. Thus, the sequential establishment of the gnathostome body plan is inherently related to the history of genomic duplication events. In this review, recent molecular developmental and evolutionary molecular research on the living lampreys are summarized and discussed, taking vertebrate comparative morphology and embryology into consideration.

Animals↗

PubMed1988

Characterization of genes which are transiently expressed during the preaggregative phase of development of Dictyostelium discoideum.

We have identified and characterized three genes, the I genes (I for induced), which are induced during the preaggregative phase of the developmental program of Dictyostelium discoideum. None of these genes are expressed in cells growing vegetatively on bacteria or in axenic broth, and their induction during early development is due to transcriptional activation. Developmental expression of I6, I8, and I11 occurs even in the absence of protein synthesis. Their induction is very rapid and occurs essentially at the onset of development. The expression is transient, peaking between 2 and 4 hr followed by a rapid loss of expression. These characteristics suggest that the induction of I6, I8, and I11 is a primary result of the initiation of development, and thus they represent the first such genes isolated. Although their expression behavior shares these characteristics, examination of their expression under various conditions of development and in a variety of aggregation-deficient mutant strains reveals that the details of the regulation and developmental control of these three genes are distinct.

Cyclic AMP↗

PubMed2000

Morphological patterns of death by myocytes in arrhythmogenic right ventricular dysplasia.

There are two forms of nuclear loss from eukaryotic cells: biochemical DNA degradation in apoptosis and nuclear extrusion from the cell body as seen in mammalian erythroblasts. In biopsies of right ventricular myocardium from 8 patients with arrhythmogenic right ventricular dysplasia (ARVD), we found not only a terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick-end labeling (TUNEL)-positive nucleus in mononuclear myocytes, but also 1 or 2 TUNEL-positive nuclei in multinuclear myocytes. With electron microscopy, we found a nuclear dislocation to the cell periphery, followed by its extrusion into the extracellular space. Both the migration and extrusion of the nuclei of myocytes resemble the morphogenesis of human erythroblasts. Nuclear extrusion from myocytes may be another form of programmed cell death. In support of this possibility, we also found evidence of cytoplasmic degradation in right ventricular myocytes from our ARVD cases, a process similar to one often seen in developmental programmed cell death and differing from typical nuclear apoptosis. In our ARVD cases, we thus found several different patterns of cell death, all associated with initial preservation of the plasmalemma and avoidance of local inflammation. All these features may be different responses to common signals for selective non-necrotic (apoptotic) death of right ventricular myocytes.

Adult↗

PubMed1984

Developmental coaching of the Down syndrome infant.

Proprioceptive input appropriate to the developmental level of the Down Syndrome infant, and kinesthetic and proprioceptive leading of the infant enhance joint stability and prompt the infant to participate in a fuller repertoire of exploratory movement at a relatively early developmental age. Comparison of performances of the Down Syndrome population at the Ray Graham-Fairwood School with that of other Down Syndrome infants in the literature suggested that our intervention program, developmental coaching, had made a difference. A retrospective study was undertaken to document the progress made. Of the 40 infants studied, 95 percent achieved certain hand skills criteria by 10 months of age; 92.5 percent achieved prewalking mobility by 10 months of age; and 40 percent achieved free walking by 18 months of age.

Activities of Daily Living↗

PubMed1980

Cellular regulation of fetal hemoglobin production.

In this paper, we put together several observations from studies in erythroid cultures that suggest that the major regulatory events determining Hb F and Hb A formation in the red cells are taken at the level of erythroid stem cells. We outlined the evidence that suggests that the program of Hb F expression changes during the differentiation of the primitive progenitors, known as burst-forming units, and we raised several possibilities on how this differentiation-dependent change in developmental programs could be accomplished. Although many questions remain still unanswered, the work done so far suggests that the mechanisms of regulation of Hb F at the cellular level can be successfully probed with existing methodologies. Delineation of the cellular mechanism of Hb F regulation is required in order to find out whether the therapeutic manipulation of Hb F in the patient with Cooley's anemia is possible or not.

Animals↗

PubMed2003

Committing embryonic stem cells to differentiate into thyrocyte-like cells in vitro.

The derivation of thyrocyte-like cells in culture is of importance in the basic study of early thyroid embryogenesis and the generation of an unlimited clinical source of thyrocytes for genetic manipulation and cell transplantation. We have established an experimental system, which shows that 6-d-old embryoid bodies (EBs) differentiated from mouse embryonic stem (ES) cells expressed a set of genes traditionally associated with thyroid cells. The genes analyzed included the thyroid transcription factor PAX8, the Na(+)/I(-) symporter, thyroperoxidase, thyroglobulin, and the TSH receptor (TSHR). Immunofluorescent analysis demonstrated the presence of TSHR-positive cells as outgrowths from 8-d-old EBs cultured on chamber slides. Accordingly, this area of cells also expressed PAX8 and another thyroid transcription factor TTF2. Of importance, TSH, the main regulator of the thyroid gland, was necessary to maintain the expression of PAX8 and TSHR genes during EB differentiation. Furthermore, thyroid-specific function, such as cAMP generation by TSH, was maintained in this model. Together, these results suggested that the developmental program associated with thyrocyte development is recapitulated in the ES/EB model system. The differentiation of mouse ES cells into thyrocyte-like cells provides a powerful model for the study of thyrocyte developmental diseases associated with this lineage and contributes to the development of thyroid hormone-secreting cell lines.

Animals↗

PubMed2005

The induction of the mating program in the phytopathogen Ustilago maydis is controlled by a G1 cyclin.

Our understanding of how cell cycle regulation and virulence are coordinated during the induction of fungal pathogenesis is limited. In the maize smut fungus Ustilago maydis, pathogenesis and sexual development are intricately interconnected. Furthermore, the first step in the infection process is mating, and this is linked to the cell cycle. In this study, we have identified a new G1 cyclin gene from U. maydis that we have named cln1. We investigated the roles of Cln1 in growth and differentiation in U. maydis and found that although not essential for growth, its absence produces dramatic morphological defects. We provide results that are consistent with Cln1 playing a conserved role in regulating the length of G1 and cell size, but also additional morphological functions. We also present experiments indicating that the cyclin Cln1 controls sexual development in U. maydis. Overexpression of cln1 blocks sexual development, while its absence enables the cell to express sexual determinants in conditions where wild-type cells were unable to initiate this developmental program. We conclude that Cln1 contributes to negative regulation of the timing of sexual development, and we propose the existence of a negative crosstalk between mating program and vegetative growth that may help explain why these two developmental options are incompatible in U. maydis.

Cyclic AMP-Dependent Protein Kinases↗

PubMed2006

Oocyte-secreted factors enhance oocyte developmental competence.

The capacity of fully grown oocytes to regulate their own microenvironment by paracrine factors secreted by the oocyte (oocyte-secreted factors, OSFs) may in turn contribute to oocyte developmental competence. Here, we investigated if OSFs have a direct influence on oocyte developmental competence during in vitro maturation (IVM). Bovine cumulus-oocyte complexes (COCs) were aspirated from abattoir-derived ovaries and matured in serum-free medium. COCs were either co-cultured with denuded oocytes (DOs) or treated with specific OSFs: recombinant bone morphogenetic protein 15 (BMP15) and/or growth differentiation factor 9 (GDF9). Following maturation, embryos were fertilized and cultured in vitro and blastocyst development and cell number were assessed on day 8. Co-culturing intact COCs with DOs did not affect cleavage rate, but increased (P<0.001) the proportion of cleaved embryos that reached the blastocyst stage post-insemination from 39% to 51%. OSFs also altered blastocyst cell allocation as co-culture of COCs with DOs significantly increased total and trophectoderm cell numbers, compared to control COCs. BMP15 alone, GDF9 alone or the two combined all (P<0.05) increased the proportion of oocytes that reached the blastocyst stage post-insemination from 41% (controls) to 58%, 50% and 55%, respectively. These results were further verified in neutralization experiments of the exogenous growth factors and of the native OSFs. Follistatin and the kinase inhibitor SB-431542, which antagonize BMP15 and GDF9, respectively, neutralized the stimulatory effects of the exogenous growth factors and impaired the developmental competence of control COCs. These results demonstrate that OSFs, and particularly BMP15 and GDF9, enhance oocyte developmental competence and provide evidence that OSF regulation of the COC microenvironment is an important determinant of oocyte developmental programming.

Animals↗

PubMed1995

Murine B cell development: commitment and progression from multipotential progenitors to mature B lymphocytes.

B lymphocytes, the cellular source of antibody, are critical components of the immune response. They develop from multipotential stem cells, progressively acquiring the traits that allow them to function as mature B lymphocytes. This developmental program is dependent on appropriate interactions with the surrounding environment. These interactions, mediated by cell-cell and cell-matrix interactions, provide the growth and differentiation signals that promote progression along the developmental pathway. This chapter addresses the properties of developing B lineage cells and the nature of the environmental signals that support B lineage progression.

Animals↗

PubMed1993

Delayed internucleosomal DNA fragmentation in programmed cell death.

DNA fragmentation was evaluated in three instances of programmed cell death, interdigital cell death in embryonic mouse limbs, and metamorphic death of both the labial glands and intersegmental muscle in the tobacco hornworm Manduca sexta. In the mouse, we evaluated both developmental cell death and expanded-range cell death induced by retinoic acid. The status of DNA was examined in several ways. Nuclei were examined by electron microscopy and Feulgen staining. Quantitative assessment of total DNA content in Feulgen-stained degenerating nuclei was made for the gland. In the labial gland, DNA content does not drop during the early phases of cell death; nor is an endonucleolytic ladder seen when DNA was examined by ethidium bromide staining or prelabeling with [3H]thymidine. Only by using end labeling of DNA could we detect DNA fragmentation at a very late stage in cell death, day 4 of the collapse of the gland. In contrast, WEHI 7.1 lymphoma cells display an early and extensive ladder after treatment with glucocorticoids. In mouse limb, for which cell death follows a more classic apoptotic morphology, a ladder is likewise not seen. We conclude that activation of an endonuclease is neither a trigger nor a necessary or defining component of the early phases of developmental programmed cell death, and that reported failure by others to find such a ladder may depend on limitations in the system that is under investigation.

Animals↗

PubMed1998

Developmental regulation of heterochromatin-mediated gene silencing in Drosophila.

The roles of differentiation, mitotic activity and intrinsic promoter strength in the maintenance of heterochromatic silencing were investigated during development using an inducible lacZ gene as an in vivo probe. Heterochromatic silencing is initiated at the onset of gastrulation, approximately 1 hour after heterochromatin is first visible cytologically. A high degree of silencing is maintained in the mitotically active imaginal cells from mid-embryogenesis until early third instar larval stage, and extensive relaxation of silencing is tightly associated with the onset of differentiation. Relaxation of silencing can be triggered in vitro by ecdysone. In contrast, timing and extent of silencing at both the initiation and relaxation stages are insensitive to changes in cell cycle activity, and intrinsic promoter strength also does not influence the extent of silencing by heterochromatin. These data suggest that the silencing activity of heterochromatin is developmentally programmed.

Animals↗

PubMed2005

The UNC-3 Olf/EBF protein represses alternate neuronal programs to specify chemosensory neuron identity.

Neuronal identities are specified by the combinatorial functions of activators and repressors of gene expression. Members of the well-conserved Olf/EBF (O/E) transcription factor family have been shown to play important roles in neuronal and non-neuronal development and differentiation. O/E proteins are highly expressed in the olfactory epithelium, and O/E binding sites have been identified upstream of olfactory genes. However, the roles of O/E proteins in sensory neuron development are unclear. Here we show that the O/E protein UNC-3 is required for subtype specification of the ASI chemosensory neurons in Caenorhabditis elegans. UNC-3 promotes an ASI identity by directly repressing the expression of alternate neuronal programs and by activating expression of ASI-specific genes including the daf-7 TGF-beta gene. Our results indicate that UNC-3 is a critical component of the transcription factor code that integrates cell-intrinsic developmental programs with external signals to specify sensory neuronal identity and suggest models for O/E protein functions in other systems.

Animals↗

PubMed2004

Genomic identification of direct target genes of LEAFY.

The switch from vegetative to reproductive development in plants necessitates a switch in the developmental program of the descendents of the stem cells in the shoot apical meristem. Genetic and molecular investigations have demonstrated that the plant-specific transcription factor and meristem identity regulator LEAFY (LFY) controls this developmental transition by inducing expression of a second transcription factor, APETALA1, and by regulating the expression of additional, as yet unknown, genes. Here we show that the additional LFY targets include the APETALA1-related factor, CAULIFLOWER, as well as three transcription factors and two putative signal transduction pathway components. These genes are up-regulated by LFY even when protein synthesis is inhibited and, hence, appear to be direct targets of LFY. Supporting this conclusion, cis-regulatory regions upstream of these genes are bound by LFY in vivo. The newly identified LFY targets likely initiate the transcriptional changes that are required for the switch from vegetative to reproductive development in Arabidopsis.

Genome, Plant↗