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At least 37 records · Page 2Linked to original sources
PubMed1993

The role of a Drosophila POU homeo domain gene in the specification of neural precursor cell identity in the developing embryonic central nervous system.

The Drosophila embryonic central nervous system (CNS) is derived from a stereotypic array of progenitor stem cells called neuroblasts (NBs). Each of the approximately 25 NBs per hemisegment undergoes repeated asymmetric divisions to produce, on average, 5-10 smaller ganglion mother cells (GMCs); each GMC, in turn, divides to produce two neurons. We demonstrate that the protein product encoded by a POU homeo domain gene (dPOU28/pdm-2) is expressed in the cell nuclei of a subset of NBs and GMCs. In the wild-type animal, GMC-1 is the only identified cell in the NB4-2 lineage that expresses dPOU28 protein to a high level, and it divides to produce the RP2 neuron and a second cell of unknown fate. Our results suggest that the presence of ectopically induced dPOU28/pdm-2 protein in the progeny of GMC-1 is sufficient to cause both of these cells to adopt their parental GMC-1 cell fate, leading to duplication of the RP2 neuron (and its sister cell) on the basis of both immunological and morphological criteria. These observations clearly implicate a role for dPOU28/pdm-2 in the specification of GMC-1 cell identity in the NB4-2 lineage and possibly in the specification of cell fate in other NB lineages in the developing embryonic CNS.

Animals↗
PubMed2003

Combined use of confocal laser scanning microscopy and transmission electron microscopy for visualisation of identical cells processed by cryotechniques.

Successive visualisation of identical plant cells by light and electron microscopy is reported. For this purpose segments of pea and barley leaves were prepared by high-pressure freezing, freeze-substitution, and low-temperature embedding. The use of Safranin O during low-temperature dehydration allowed, on one hand, staining of all cellular components as investigated by confocal laser scanning microscopy and, on the other hand, excellent ultrastructural and antigenic preservation. A newly constructed specimen holder enabled precise relocation of the target cells for electron microscopic investigations. Transmission electron microscopy and immunohistochemistry revealed that during the whole procedure the ultrastructure of the cells as well as the antigenicity of cell constituents were preserved.

Cryoelectron Microscopy↗
PubMed1994

Immortalizing oncogenes subvert the establishment of granule cell identity in developing cerebellum.

After implantation into the external germinal layer of early postnatal cerebellum, primary external germinal layer progenitor cells gave rise exclusively to granule neurons. In contrast, all major classes of cerebellar cells were observed following implantation of embryonic day 13 cerebellar precursor cells into the external germinal layer. These results suggest that granule cells arise from precursors with a restricted potential. In contrast to results with the primary external germinal layer population, cell lines established from external germinal layer cells, by infection with a retrovirus containing the SV40 large T-antigen oncogene, gave rise to several cerebellar cell types upon implantation. These included granule neurons, one subclass of stellate interneurons, Golgi cells, Bergmann glia and astrocytes. From these results, we conclude that early postnatal external germinal layer progenitors are normally fated to a granule cell identity and that expression of the SV40 large T-antigen oncogene subverts mechanisms that control granule neuron fate.

Animals↗
PubMed2004

Retinoic-acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells.

Retinoic acid (RA) is one of the most important morphogens, and its embryonic distribution correlates with neural differentiation and positional specification in the developing central nervous system. To investigate the concentration-dependent effects of RA on neural differentiation of mouse embryonic stem cells (ES cells), we investigated the precise expression profiles of neural and regional specific genes by ES cells aggregated into embryoid bodies (EBs) exposed to various concentrations of RA or the BMP antagonist Noggin. RA promoted both neural differentiation and caudalization in a concentration-dependent manner, and the concentration of RA was found to regulate dorso-ventral identity, i.e., higher concentrations of RA induced a dorsal phenotype, and lower concentrations of RA induced a more ventral phenotype. The induction of the more ventral phenotype was due to the higher expression level of the N-terminus of sonic hedgehog protein (Shh-N) when treated with low concentration RA, as it was abrogated by an inhibitor of Shh signaling, cyclopamine. These findings suggest that the concentration of RA strictly and simultaneously regulates the neuralization and positional specification during differentiation of mouse ES cells and that it may be possible to use it to establish a strategy for controlling the identity of ES-cell-derived neural cells.

Animals↗
PubMed1993

Coupling of cell identity to signal response in yeast: interaction between the alpha 1 and STE12 proteins.

In Saccharomyces cerevisiae, the STE12 protein mediates transcriptional induction of cell type-specific genes in response to pheromones. STE12 binds in vitro to the pheromone response elements (PREs) present in the control region of a-specific genes. STE12 is also required for transcription of alpha-specific genes, but there is no evidence that it binds directly to these genes. Instead, the MAT alpha-encoded protein alpha 1 and the MCM1 product bind to the DNA element that is responsible for alpha-specific and a-factor-inducible expression. To explore the role of STE12 in the pheromone induction of alpha-specific genes, we cloned STE12 and MAT alpha 1 homologs from the related yeast Kluyveromyces lactis. The K. lactis STE12 protein did not cooperate with the S. cerevisiae alpha 1 protein to promote the overall mating process or the induction of transcription of an alpha-specific gene. However, introduction of both K. lactis STE12 along with K. lactis alpha 1 did restore mating, suggesting that an interaction between STE12 and alpha 1 is important for alpha-specific gene activation. We also show that bacterially expressed STE12 and alpha 1 are able to form a complex in vitro. Thus, we demonstrate a coupling in alpha cells between a protein functioning in cell identity, alpha 1, with a protein responsive to the pheromone-induced signal STE12.

Amino Acid Sequence↗
PubMed1983

T-cell hyperreactivity of NZB mice against H-2 identical cells. Equal cytotoxic T lymphocyte precursor frequency against H-2 allogeneic and H-2 syngeneic target cells in NZB.

NZB mice serve as a model for human systemic lupus erythematodes. T-cell abnormalities in this strain have previously been described. In this paper the cytotoxic T lymphocyte precursor (CTL-p) frequencies of NZB mice against H-2 allogeneic and H-2 syngeneic cells are investigated and compared with those of the normal strain BALB/c. The CTL-p frequency in NZB lymphocytes against H-2 allogeneic cells equals that in normal mouse strains (i.e. 1/7500). The NZB anti BALB/c response is in the same order of magnitude. No corresponding BALB/c anti NZB response was elicited. The results suggest abnormally high sensitivity of NZB CTL-p to helper signals.

Animals↗
PubMed2000

Large macrophage colony-forming cells identical to high proliferative potential colony-forming cells in peripheral blood of patients with collagen vascular diseases: high occurrence among patients with systemic sclerosis and dermatomyositis.

OBJECTIVE: To examine peripheral blood (PB) of patients with various collagen vascular diseases (CVD) for the presence of colony-forming cells (CFC) that form large macrophage colonies (> 2.5 mm in diameter, > 10,000 cells). METHODS: Peripheral blood mononuclear cells were obtained from 92 patients with various active CVD and 20 healthy controls, and assayed for in vitro colony formation. There were 14 patients with systemic lupus erythematosus (SLE), 30 with rheumatoid arthritis (RA), 17 with systemic sclerosis (SSc), 20 with polymyositis (PM)/dermatomyositis (DM) (11 PM, 9 DM) and 11 with systemic vasculitis. RESULTS: Large macrophage CFC were detected in PB of 7% of patients with SLE (1/14), 17% with RA (5/30), 47% with SSc (8/17), 30% with PM/DM (6/20) [9% PM (1/11) and 56% DM (5/9)], 0% of those with systemic vasculitis (0/11) and 0% of the healthy subjects (0/20). There was a significant difference between the occurrence of CFC in patients with PM versus patients with DM (p < 0.05). The occurrence of CFC in patients with SSc or DM was significantly higher than that in patients with other CVD including SLE, RA, PM, and systemic vasculitis (p < 0.05). CONCLUSION: Based on the size of the colonies they formed, the CFC corresponded to high proliferative potential colony-forming cells, a subset of primitive hematopoietic cells. Our findings among patients with CVD indicate that these primitive hematopoietic progenitor cells, which are believed to constitute a noncirculating population in healthy individuals, are found most frequently in PB of patients with SSc and DM. It is likely that primitive hematopoietic cells are frequently mobilized into the peripheral circulation during the pathogenesis of SSc and DM.

Arthritis, Rheumatoid↗
PubMed1996

Glossy15, an APETALA2-like gene from maize that regulates leaf epidermal cell identity.

Vegetative development in many plants progresses through distinct juvenile and adult phases. In maize, the transition from juvenile to adult shoot development affects a variety of leaf epidermal cell traits. These include epicuticular waxes, leaf hairs, and cell wall characteristics. Previous genetic and phenotypic analyses have shown that the maize Glossy15 (Gl15) gene is required for the expression of juvenile epidermal traits after leaf 2. We report here the molecular cloning of the Gl15 gene using a defective Suppressor-Mutator (dSpm) element insertion as a transposon-tag. Consistent with the gl15 mutant phenotype, the pattern of Gl15 mRNA expression was correlated with a juvenile leaf epidermal cell identity and was regulated by upstream factors such as Corngrass1. The Gl15 gene encodes a putative transcription factor with significant sequence similarity to the Arabidopsis regulatory genes APETALA2 and AINTEGUMENTA, which act primarily to regulate floral organ identity and ovule development. This finding expands the known functions of APETALA2-related genes to include the control of both vegetative and reproductive lateral organ identity and provides molecular support for the hypothesis that leaves and floral organs are related structures derived from a common growth plan.

Amino Acid Sequence↗
PubMed1997

Establishment of stem cell identity in the Drosophila germline.

In the adult Drosophila ovary the continuous production of eggs depends upon a small group of stem cells located at the anterior tip of the germarium. These stem cells divide asymmetrically to self renew and to generate a cystoblast, which in females is committed to the oocyte differentiation pathway. While much is known about the development of poststem cell cystoblasts, little is known about when stem cells are formed or how their identity is initially established. To investigate these questions we have used the P-M hybrid dysgenesis syndrome as a tool for ablating the "pre-stem cell" progenitors of the stem cells. Our experiments indicate that the pre-stem cells in females assume stem cell identity during the early pupal stage. Our results also suggest a model in which at least two pre-stem cells must be present within an ovariole for the specification of stem cell fate. When only a single pre-stem cell is sequestered by an ovariole, this cell does not assume stem cell identity, but instead follows the cystoblast-cystocyte differentiation pathway.

Animals↗
PubMed1997

Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-beta gene families.

We have examined whether the development of embryonic muscle fiber type is regulated by competing influences between Hedgehog and TGF-beta signals, as previously shown for development of neuronal cell identity in the neural tube. We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite. Ectopic expression in the notochord of Dorsalin-1, a member of the TGF-beta superfamily, inhibits the formation of muscle pioneer cells, demonstrating that TGF-beta signals can antagonize the induction of muscle pioneer cells by Hedgehog. We propose that a Hedgehog signal first induces the formation of slow muscle precursor cells, and subsequent Hedgehog and TGF-beta signals exert competing positive and negative influences on the development of muscle pioneer cells.

Animals↗
PubMed1988

Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature.

Three women, 51-69 years of age with carcinomas of the urinary bladder or ureter, had ovarian tumors of identical cell types 2 to 7 years apart. In two cases the tumors were transitional-cell carcinomas and in the third case, signet-ring-cell carcinomas. It was difficult in the cases of transitional-cell carcinoma to determine whether the ovarian tumors were metastatic or independent primary tumors. Consideration of a variety of features of our two cases and of four similar cases reported in the literature led us to the conclusion that the ovarian tumors were probably metastatic in one case, probably primary in two cases, and of unknown nature in three cases, but some degree of doubt existed in all the cases. The signet-ring-cell tumor in the ovary had the typical features of a Krukenberg tumor. Four of 11 women with signet-ring-cell carcinomas of the bladder have had ovarian metastases.

Adenocarcinoma, Mucinous↗
PubMed2005

Hedgehog signalling and the specification of muscle cell identity in the zebrafish embryo.

Signalling by members of the Hedgehog family of secreted proteins plays a central role in the development of many animal species. In the zebrafish embryo, the specification of myoblast fates is controlled by Hedgehog signals emanating from axial midline structures. Distinct muscle cell identities are induced by varying levels of signalling activity. The SET domain transcription factor, Blimp1, is a key target of Hedgehog signalling in this process.

Animals↗
PubMed2006

Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants.

Although the secreted molecule Fgf8 is a key player of the isthmic organiser function, the mechanisms by which it acts remain unclear. Here, we present evidence indicating that Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory. We first show that, as in mouse, lack of Otx function in zebrafish leads to transformation of the presumptive mesencephalon into an extended rhombomere 1 (r1). Expanded Fgf8 expression was proposed to be the cause of this fate transformation. However, this report demonstrates that zebrafish embryos lacking both Otx and fgf8 functions retain an extended r1 and display differentiation of at least two cerebellar cell fates. We show that this is not caused by presence of other Fgfs, which implies that in absence of Otx, Fgf function is not necessary for the differentiation of cerebellar cell types. Otx proteins are therefore potent repressors of cerebellar fates, kept out of r1 progeny by Fgf8. Because Otx transcripts are not present in presumptive r1 territory prior to fgf8 expression, Fgf8 is required to maintain, rather than induce, the posterior boundary of Otx expression. This maintenance is enough to allow cerebellar differentiation.

Animals↗
PubMed2003

Multiple muscle cell identities induced by distinct levels and timing of hedgehog activity in the zebrafish embryo.

BACKGROUND: In the zebrafish embryo, the differentiation of distinct muscle fiber types has been shown to require the activity of members of the Hedgehog (Hh) family of secreted proteins. Evidence from other systems suggests that Hh behaves as a morphogen, inducing cell fates in a concentration-dependent manner. Exactly how Hh signaling contributes to the generation of the correct pattern of cells within the zebrafish myotome, however, has remained obscure. RESULTS: Here, we distinguish four distinct myotomal cell identities in the zebrafish embryo on the basis of their position, morphology, and gene expression patterns. Using morpholino oligonucleotides (MOs) to diminish the activities of the Hh pathway components Patched (Ptc), Fused (Fu), and Suppressor of Fused (Su(fu)), and the teratogen cyclopamine to inhibit the Hh transducer Smoothened (Smo), we show that the appropriate differentiation of each cell type depends upon the levels and range of Hh signaling within the myotome. In addition, by transiently modulating Hh activity by using cyclopamine and a heat-inducible transgene, we demonstrate that the competence of myotomal cells to respond to Hh changes with time. Finally, we show that the Gli1 and Gli2 transcription factors mediate most of the response of myotomal cells to Hh. CONCLUSIONS: Hh signaling acts in a dosage-dependent manner to specify cell fate in the zebrafish myotome. Allocation of the correct number of cells to a specific fate depends upon the range of Hh activity. The timing of exposure to Hh determines the response of cells to the signal.

Animals↗
PubMed2006

The turnip mutant of Arabidopsis reveals that LEAFY COTYLEDON1 expression mediates the effects of auxin and sugars to promote embryonic cell identity.

The transition from embryonic to vegetative growth marks an important developmental stage in the plant life cycle. The turnip (tnp) mutant was identified in a screen for modifiers of POLARIS expression, a gene required for normal root growth. Mapping and molecular characterization of tnp shows that it represents a gain-of-function mutant of LEAFY COTYLEDON1 (LEC1), due to a promoter mutation. This results in the ectopic expression of LEC1, but not of other LEC genes, in vegetative tissues. The LEC class of genes are known regulators of embryogenesis, involved in the control of embryonic cell identity by currently unknown mechanisms. Activation of the LEC-dependent pathway in tnp leads to the loss of hypocotyl epidermal cell marker expression and loss of SCARECROW expression in the endodermis, the ectopic accumulation of starch and lipids, and the up-regulation of early and late embryonic genes. tnp also shows partial deetiolation during dark growth. Penetrance of the mutant phenotype is strongly enhanced in the presence of exogenous auxin and sugars, but not by gibberellin or abscisic acid, and is antagonized by cytokinin. We propose that the role of LEC1 in embryonic cell fate control requires auxin and sucrose to promote cell division and embryonic differentiation.

1-Phosphatidylinositol 4-Kinase↗
PubMed2006

Activator protein-1 activity regulates epithelial tumor cell identity.

To examine the consequences of inhibiting activator protein-1 (AP-1) transcription factors in skin, transgenic mice were generated, which use the tetracycline system to conditionally express A-FOS, a dominant negative that inhibits AP-1 DNA binding. Older mice develop mild alopecia and hyperplasia of sebaceous glands, particularly around the eyes. When A-FOS was expressed during chemical-induced skin carcinogenesis, mice do not develop characteristic benign and malignant squamous lesions but instead develop benign sebaceous adenomas containing a signature mutation in the H-ras proto-oncogene. Inhibiting AP-1 activity after tumor formation caused squamous tumors to transdifferentiate into sebaceous tumors. Furthermore, reactivating AP-1 in sebaceous tumors results in a reciprocal transdifferentiation into squamous tumors. In both cases of transdifferentiation, individual cells express molecular markers for both cell types, indicating individual tumor cells have the capacity to express multiple lineages. Molecular characterization of cultured keratinocytes and tumor material indicates that AP-1 regulates the balance between the wnt/beta-catenin and hedgehog signaling pathways that determine squamous and sebaceous lineages, respectively. Chromatin immunoprecipitation analysis indicates that c-Jun binds several wnt promoters, which are misregulated by A-FOS expression, suggesting that members of the wnt pathway can be a primary targets of AP-1 transcriptional regulation. Thus, AP-1 activity regulates tumor cell lineage and is essential to maintain the squamous tumor cell identity.

Adenocarcinoma, Sebaceous↗
PubMed1990

Methods of successive multiparametric cytochemistry and microfluorometry on identical cells with special reference to cell cycle phases in a chick embryo.

The study of cell cycle kinetics in relation to regulatory mechanisms in embryonic development is considered quite important, but many technical difficulties still remain owing to the complexity of embryonic systems. To facilitate such study, a novel method of multiparametric microfluorometry was developed and is presented here. In many other multiparametric methods, various cytochemistries and fluorometries are conducted at the same time, whereas in our system only one type of cytochemistry and its microfluorometry are performed first and then other types subsequently. Our system is composed of two parts, a method for combining various types of quantitative cytochemistries to be performed in succession on identical cells and a method that permits the implementation of cytochemistries and microfluorometries in succession using in combination a microfluorometer, TV camera, video recorder, digital Telopper, and microcomputers. A method for the evaluation and normalization of microfluorometric data on DNA content is described. The cell cycle phases of each cell can be accurately distinguished on the basis of DNA content and BrdU uptake, using a statistical method. A cell cycle traverse study using embryonic avian scale dermal cells was carried out in which the four parameters of DNA content, double labeling with BrdU and [3H]AdR, and time lapse between the two labelings were included. As an example of its application to molecular cytochemistry, in situ nick translation was conducted on developing scale dermal cells. The special features and scope of application of the present system are discussed.

Animals↗
PubMed1990

Microtubule-associated-protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells.

Treatment of PC12 cells with either nerve growth factor (NGF), a differentiating factor, or epidermal growth factor (EGF), a mitogen, resulted in 7-15-fold activation of a protein kinase activity in cell extracts that phosphorylated microtubule-associated protein (MAP) 2 on serine and threonine residues in vitro. Both the NGF-activated kinase and the EGF-activated kinase could be partially purified by sequential chromatography on DEAE-cellulose, phenyl-Sepharose and hydroxylapatite, and were identical with each other in their chromatographic behavior, apparent molecular mass (approximately 40 kDa) on gel filtration, substrate specificity, and phosphopeptide-mapping pattern of MAP2 phosphorylated by each kinase. Moreover, both kinases were found to be indistinguishable from a mitogen-activated MAP kinase previously described in growth-factor-stimulated or phorbol-ester-stimulated fibroblastic cells, based on the same criteria. Kinase assays in gels after SDS/polyacrylamide gel electrophoresis revealed further that the NGF- or EGF-activated MAP kinase in PC12 cells, as well as the EGF-activated MAP kinase in fibroblastic 3Y1 cells resided in two closely spaced polypeptides with an apparent molecular mass of approximately 40 kDa. In addition, these MAP kinases were inactivated by either acid phosphatase treatment or protein phosphatase 2A treatment. These results indicate that MAP kinase may be activated through phosphorylation by a differentiating factor as well as by a mitogen. MAP kinase activation by EGF was protein kinase C independent; it reached an almost maximal level 1 min after EGF treatment and subsided rapidly within 30-60 min. On the other hand, NGF-induced activation of MAP kinase was partly protein kinase C dependent and continued for at least 2-3 h.

Adrenal Gland Neoplasms↗