Biomedical subjects

G D Paterno

Publications and source records attributed to G D Paterno.

24 records · Page 2Linked to original sources

PubMed1989

The role of fibroblast growth factor in early Xenopus development.

In early amphibian development, the mesoderm is formed around the equator of the blastula in response to an inductive signal from the endoderm. A screen of candidate substances showed that a small group of heparin-binding growth factors (HBGFs) were active as mesoderm-inducing agents in vitro. The factors aFGF, bFGF, kFGF and ECDGF all show similar potency and can produce inductions at concentrations above about 100 pM. The product of the murine int-2 gene is also active, but with a lower specific activity. Above the induction threshold there is a progressive increase of muscle formation with dose. Single blastula ectoderm cells can be induced and will differentiate in a defined medium to form mesodermal tissues. All inner blastula cells are competent to respond to the factors but outer cells, bearing oocyte-derived membrane, are not. Inducing activity can be extracted from Xenopus blastulae and binds to heparin like the previously described HBGFs. Antibody neutralization and Western blotting experiments identify this activity as bFGF. The amounts present are small but would be sufficient to evoke inductions in vivo. It is not yet known whether the bFGF is localized to the endoderm, although it is known that inducing activity secreted by endodermal cells can be neutralized by heparin. The competence of ectoderm to respond to HBGFs rises from about the 128-cell stage and falls again by the onset of gastrulation. This change is paralleled by a rise and fall of binding of 125I-aFGF. Chemical cross-linking reveals that this binding is attributable to a receptor of relative molecular mass about 130 x 10(3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

An embryonic DNA-binding protein specific for a region of the human IFN beta 1 promoter.

Embryonal carcinoma (EC) cells are unable to make interferon in response to inducing agents. This block disappears after differentiation. We have found that nuclear extracts from undifferentiated P19 EC cells contain a DNA-binding activity which specifically recognizes a region within the human interferon-beta 1 promoter. This activity is absent from differentiated cell types, both of EC and non-EC origin. The binding of the factor in undifferentiated EC cells leads to dramatic changes in the overall protein binding pattern of the interferon promoter as compared with differentiated cells, and may be responsible for repression of the endogenous interferon-beta gene prior to differentiation.

Animals↗

PubMed1987

Isolation and characterisation of a murine cDNA clone highly homologous to the yeast L29 ribosomal protein gene.

We report here the isolation of a murine cDNA clone (cCL3) which is homologous to the mRNA of the yeast ribosomal protein L29. Comparison of the deduced amino-acid composition of cCL3 to those known for rat ribosomal proteins indicates that this cDNA codes for mammalian ribosomal protein L27'. The gene corresponding to the cDNA is present at approximately 15 copies per genome, some of these probably representing processed pseudogenes. The cDNA hybridizes to an mRNA of 600 nucleotides from various mammals at high stringency, and to an avian transcript of the same size at low stringency. It has been suggested that L29 is involved in peptidyl transferase activity. The strong homology of mammalian L27' to yeast L29 suggests a function which has been conserved throughout evolution, and thus L27' may also be involved in peptidyl transferase activity.

Amino Acid Sequence↗

PubMed1985

X chromosome reactivation in mouse embryonal carcinoma cells.

The embryonal carcinoma cell line, C86S1, carries two X chromosomes, one of which replicates late during S phase of the cell cycle and appears to be genetically inactive. C86S1A1 is a mutant which lacks activity of the X-encoded enzyme, hypoxanthine phosphoribosyltransferase (HPRT). Treatment of C86S1A1 cells with DNA-demethylating agents, such as 5-azacytidine (5AC), resulted in (i) the transient expression in almost all cells of elevated levels of HPRT and three other enzymes encoded by X-linked genes and (ii) the stable expression of HPRT in up to 5 to 20% of surviving cells. Most cells which stably expressed HPRT had two X chromosomes which replicated in early S phase. C86S1A1 cells which had lost the inactive X chromosome did not respond to 5AC. These results suggest that DNA demethylation results in the reactivation of genes on the inactive X chromosome and perhaps in the reactivation of the entire X chromosome. No such reactivation occurred in C86S1A1 cells when the cells were differentiated before exposure to 5AC. Thus, the process of X chromosome inactivation may be a sequential one involving, as a first step, methylation of certain DNA sequences and, as a second step, some other mechanism(s) of transcriptional repression.

Animals↗

PubMed1985

X chromosome inactivation during induced differentiation of a female mouse embryonal carcinoma cell line.

P10 is a line of embryonal carcinoma cells with a euploid female karyotype. By making use of variant alleles of X-linked genes and of cytogenetic procedures, we have previously shown that the P10 cells have two genetically active X chromosomes. We show here that P10 cells rapidly differentiate into a cell type resembling extraembryonic endoderm when cultured in the presence of retinoic acid. This differentiation is accompanied by X chromosome inactivation as determined by the appearance of a late-replicating X chromosome. Analysis of the X-linked variant alleles indicated that the P10-derived endoderm did not preferentially inactivate paternally derived X chromosomes. This result is in contrast to the situation in normal extraembryonic endoderm, and suggests that the X inactivation process in differentiating P10 cultures resembles that which occurs in normal embryonic rather than extraembryonic tissues.

Animals↗

PubMed1981

Cellular differentiation and pattern formation in the absence of morphogenesis in the cellular slime mould Polysphondylium pallidum: evidence for a biochemical tip (organizer) in submerged aggregates.

When amoebae of Polysphondylium pallidum WS320 are placed in nonnutrient buffer in roller tube culture they form spherical or ellipsoidal aggregates. At first the aggregates demonstrate a "loose" morphology but by 12 h, with the formation a a cellulose-containing, peripheral sheath, they become "tight" aggregates. At this time stalk differentiation begins. Using various methods for the resolution of prespore (ultrastructure, spore antigen immunofluorescence, periodic acid - Schiff staining) and prestalk (ultrastructure, alkaline phosphatase histochemistry, neutral red staining, Calcofluor fluorescence) cell localization, the pattern of cell differentiation in submerged aggregates was shown to be essentially identical to that of normal pseudoplasmodia. Furthermore, using a cAMP bioassay it was revealed that the submerged aggregates, while devoid of a morphological tip, do possess a biochemical tip which is correlated with sites of neutral red staining and stalk cell differentiation. As a result of these studies, an earlier argument that the tip of the pseudoplasmodium is not essential for the establishment of pattern or in the "organization" of cellular differentiation during slime mould development is contradicted.

Alkaline Phosphatase↗