PubMed Health⌕ Search

Biomedical subjects

G R Dressler

Publications and source records attributed to G R Dressler.

17 recordsLinked to original sources
PubMed1995

Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides.

Renal cell carcinoma (RCC) is the most common malignancy in the adult kidney. Because RCC is generally thought to arise from the epithelium of the proximal tubules, the expression of Pax-2, a gene required for renal epithelium development, was examined in primary tumors and tumor-derived cell lines. Immunostaining of frozen sections from the primary tumors indicated Pax-2 expression in the malignant cells but not in the surrounding stroma. In a panel of human RCC-derived cell lines, 73% expressed Pax-2 protein and mRNA. Treatment of RCC cell lines with antisense oligodeoxynucleotides resulted in down-regulation of Pax-2 protein expression and growth inhibition after 3 days in culture. These data indicate that Pax-2 gene function is required for proliferation, as well as differentiation during embryonic development, and suggest a novel therapy for RCC.

Base Sequence↗
PubMed1995

The genetic control of renal development.

The molecular basis of the organogenesis of the mammalian kidney is being investigated at multiple levels, with several exciting developments. Cellular signaling during and after kidney induction may be mediated in part by Wnt genes, which encode secreted, matrix-associated peptides. The Wilms' tumor suppressor gene WT1 is required for the kidney mesenchyme to respond to induction; the transcription factor Pax-2 may regulate the aggregation and proliferation of the kidney mesenchyme immediately after induction. Although the links between signaling molecules, their receptors, and the activation and repression of transcription factors in the kidney remain to be determined, several key elements of the genetic cascade driving kidney morphogenesis are now characterized.

Animals↗
PubMed1995

Transcription factors in renal development: the WT1 and Pax-2 story.

The development of a complex, multicellular organ, such as the kidney, from two embryonic progenitor tissues requires the activation and suppression of transcription factors that regulate tissue and cell type-specific gene expression. From areas as diverse as fruit fly development and human cancer genetics, a number of important genes have been identified that help to orchestrate the early events of renal epithelium induction and differentiation. The Wilms' tumor-suppressor gene WT1 is critical for regulating the early response of the kidney mesenchyme to induction and may play multiple roles during the course of renal epithelial cell development and tumor formation. The Pax-2 gene is activated in the mesenchyme after induction and is necessary for condensation and perhaps proliferation of the induced cells. How these two important gene products exert their effects will be discussed in light of recent evidence on DNA binding, transcription repression, and protein interactions.

Animals↗
PubMed1992

Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor.

The murine Pax-2 gene contains a protein coding domain homologous to the Drosophila paired-box, first described in certain developmental control genes of the segmentation type. Polyclonal antibodies recognize two Pax-2 proteins that are encoded by differentially spliced mRNAs. The Pax-2 proteins can bind a DNA sequence known to interact with the paired domain of a Drosophila protein. By immunocytochemistry, expression of Pax-2 could be localized to the nuclei of condensing mesenchyme cells and their epithelial derivatives in the developing kidney. Expression is abruptly down-regulated as the tubular epithelium differentiates. High levels of Pax-2 expression could also be detected in the epithelial cells of human Wilms tumors. These data suggest that Pax-2 is a transcription factor active during the mesenchyme-to-epithelium transition in early kidney development and in Wilms tumor.

Animals↗
PubMed1992

Comparative analysis of Pax-2 protein distributions during neurulation in mice and zebrafish.

Members of different vertebrate species share a number of developmental mechanisms and control genes, suggesting that they have similar genetic programs of development. We compared the expression patterns of the Pax-2 protein in Mus musculus and Brachydanio rerio to gain a better understanding of the evolution of developmental control genes. We found that the tissue specificity and the time course of Pax-2 expression relative to specific developmental processes are remarkably similar during the early development of the two organisms. The brain, the optic stalk, the auditory vesicle, the pronephros, and single cells in the spinal cord and the hindbrain express Pax-2 in both species. The Pax-2 expression domain in the prospective brain of E8 mouse embryos has not been described previously. Expression appears first during early neurulation at the junction between the midbrain and hindbrain. However, there are some differences in Pax-2 expression between the two species. Most notable, expression at the midbrain/hindbrain boundary is no longer detectable after E11 in the mouse. Using monoclonal antibodies, we could exclude that primary neurons express Pax-2 in the zebrafish spinal cord. Our results confirm that Pax genes are highly conserved both in sequences and in expression patterns, indicating that they may have a function during early development that has been conserved during vertebrate evolution.

Animals↗
PubMed1990

Oct-4: a germline-specific transcription factor mapping to the mouse t-complex.

Oct-4 is a maternally expressed octamer-binding protein encoded by the murine Oct-4 gene. It is present in unfertilized oocytes, but also in the inner cell mass and in primordial germ cells. Here we show that the ectopic expression of Oct-4 in HeLa cells is sufficient for transcriptional activation from the octamer motif, indicating that Oct-4 is a transcription factor. Therefore, Oct-4 is the first transcription factor described that is specific for the early stages of mouse development. The spatial and temporal expression patterns were further determined using in situ hybridization. With this technique Oct-4 expression is detected in the oocyte, in the blastocyst and before gastrulation in the embryonic ectoderm. After day 8 Oct-4 expression decreases and is restricted to primordial germ cells from about day 8.5 onwards. Therefore Oct-4 is a transcription factor that is specifically expressed in cells participating in the generation of the germline lineage. Linkage analysis using B X D recombinant inbred mouse strains demonstrates that Oct-4 maps to chromosome 17 in or near the major histocompatibility complex. Several mouse mutants in the distal region of the mouse t-complex affecting blastocyst and embryonic ectoderm formation also map to this region.

Animals↗
PubMed1990

Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system.

The murine genome contains multiple genes with protein domains homologous to the Drosophila paired box, present in certain segmentation genes. At least one of these murine paired box (Pax) genes is associated with a developmental mutation. This report, in conjunction with the accompanying paper, describes a second member of this gene family, Pax2, that is also expressed during embryogenesis. Two overlapping cDNA clones were isolated and sequenced. At least two forms of the Pax2 protein can be deduced from the cDNA sequence. In addition to the highly conserved paired domain, an octapeptide sequence is located downstream. Expression of Pax2 is primarily restricted to the developing embryo in the excretory and central nervous systems. The transient nature of Pax2 expression during kidney organogenesis correlates with polarization and induction of epithelial structures and may indicate an important morphogenetic role for this gene.

Amino Acid Sequence↗
PubMed1990

Spatially and temporally restricted expression of Pax2 during murine neurogenesis.

The expression of the murine paired-box-containing gene, Pax2, is examined in the developing central nervous system by in situ hybridization. Pax2 expression is detected along the boundaries of primary divisions of the neural tube. Initially, Pax2 is expressed in the ventricular zone in two compartments of cells on either side of the sulcus limitans and along the entire rhombencephalon and spinal cord. At later times, Pax2 is restricted to progeny cells that have migrated to specific regions of the intermediate zone. In the eye, Pax2 expression is restricted to the ventral half of the optic cup and stalk and later to the optic disc and nerve. In the ear, expression is restricted to regions of the otic vesicle that form neuronal components. The transient and restricted nature of Pax2 expression suggests that this murine segmentation gene homologue may also establish compartmental boundaries and contribute to the specification of neuronal identity, as do certain Drosophila segmentation genes.

Animals↗
PubMed1989

The transcription termination region of the adenovirus 2 major late transcript contains multiple functional elements.

In order to understand the process of transcription termination by eukaryotic RNA polymerase II, the transcription termination region of the advenovirus 2 major late transcription unit was analysed in a transient transfection system. Previously, it had been demonstrated that the entire sequence from map units (m.u.) 97.1 to 100 of the adenovirus 2 genome terminates transcription when inserted into the 5' or 3' untranslated sequences of the chloramphenicol acetyltransferase gene. Using subclones and Bal 31 deletion mutants of the termination region, we have shown that the termination region consists of multiple elements each capable of inhibiting gene expression independently. A DNA sequence analysis reveals the presence of a highly repetitive A-rich sequence motif throughout the entire termination region. The data suggest that the A-rich motif may mediate the transcription termination process.

Adenoviruses, Human↗
PubMed1989

Anterior boundaries of Hox gene expression in mesoderm-derived structures correlate with the linear gene order along the chromosome.

The developmental expression patterns of four genes, Hox 1.1, Hox 1.2, Hox 1.3 and Hox 3.1, were examined by in situ hybridization to serial embryonic sections. The three genes of the Hox 1 cluster, used in this study, map to adjacent positions along chromosome 6, whereas the Hox 3.1 gene maps to the Hox 3 cluster on chromosome 15. The anterior expression limits in segmented mesoderm varied among the four genes examined. Interestingly, a linear correlation exists between the position of the gene along the chromosome and the extent of anterior expression. Genes that are expressed more posterior are also more restricted in their expression in other mesoderm-derived tissues. The order of expression anterior to posterior was determined as: Hox 1.3, Hox 1.2, Hox 1.1 and Hox 3.1. Similarly, genes of the Drosophila Antennapedia and Bithorax complex specifying segment identity also exhibit anterior expression boundaries that correlate with gene position. The data suggest that Hox genes may specify positional information along the anterior-posterior axis during the formation of the body plan.

Animals↗
PubMed1988

Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development.

The mouse genome contains at least three copies of sequences homologous to the "paired box", a conserved domain in several Drosophila segmentation genes of the pair-rule and segment polarity classes. Overlapping phages were isolated from two different genomic libraries using the Drosophila gooseberry distal paired box as a probe. The hybridizing sequences are highly homologous to the conserved Drosophila paired box sequences. A single 3.1 kb Pax 1 (paired box gene) transcript was detected during embryonic development, whereas no transcripts were detected in adult tissues. Detailed in situ hybridization analyses with frozen embryonic sections demonstrated Pax 1 transcripts in the perichordal zone of the developing vertebral column. The expression pattern suggests a role for this gene in the formation of segmented structures of the mouse embryo.

Amino Acid Sequence↗
PubMed1988

Primary structure and developmental expression pattern of Hox 3.1, a member of the murine Hox 3 homeobox gene cluster.

The murine Hox 3.1 gene maps to a cluster of homeobox-containing genes on chromosome 15. We report the primary structure of the Hox 3.1 protein, as deduced from cDNA sequences, and the expression of Hox 3.1 mRNA during embryogenesis. In addition, a second member of the gene cluster, Hox 3.2, is characterized. The predicted Hox 3.1 protein consists of 242 amino acid residues and has a calculated mol. wt of 28 kd. Besides the homeodomain, it shares with other murine homeodomain proteins a conserved hexapeptide, a region rich in glutamic acid residues at the carboxy terminus and homology at the amino terminus. During embryogenesis, Hox 3.1 transcripts are detected first in the posterior neural tube of 9.5 days post-coital embryos. At later developmental stages, a ventral-dorsal gradient of Hox 3.1 transcript accumulation is established. Hox 3.1 transcripts also are detected in the thoracic sclerotomes from the 6th to the 10th thoracic pre-vertebrae. The data support the hypothesis that the Hox 3.1 gene specifies positional information during murine embryogenesis.

Amino Acid Sequence↗
PubMed1988

A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine.

A mouse gene, Cdx-1, was isolated from an embryonic cDNA library using a Drosophila caudal gene probe. The deduced amino acid sequence of Cdx-1 contains conserved sequence domains along the entire gene, as well as a highly conserved caudal-type homeo box. A structural comparison suggests a common ancestral origin of mouse Cdx-1 and Drosophila caudal. The expression of Cdx-1 during embryogenesis was analyzed by Northern blotting and in situ hybridization. Cdx-1-specific transcripts are localized in the epithelial lining of the intestines beginning at 14 days' gestation. The expression of Cdx-1 in the intestine continues into adulthood, but cannot be detected in any other tissues. The Cdx-1 gene is the first homeo-box-containing gene expressed in cells derived from the embryonic endoderm.

Amino Acid Sequence↗
PubMed1987

Latent herpes simplex virus type 1 DNA is not extensively methylated in vivo.

The methylation pattern of herpes simplex virus type 1 (HSV-1) DNA, present in the central nervous system of latently infected mice, was examined by digestion of the DNA with methylation-sensitive restriction endonucleases and Southern blot hybridization. Using the enzymes SmaI, XmaI, SalI and SacII, the data indicate no extensive methylation of latent HSV-1 DNA in vivo. Thus, extensive methylation of the viral genome is not a necessary condition for, or a consequence of maintaining, the latent state in vivo.

Animals↗
PubMed1987

DNA sequences downstream of the adenovirus type 2 fiber polyadenylation site contain transcription termination signals.

The major late transcription unit of adenovirus type 2 (Ad2) terminates in a region near the end of the linear DNA genome at map units 98.2 to 100. Specific 3' ends mapping in the transcription termination region were detected in nuclear but not cytoplasmic RNA isolated at 16 to 18 h postinfection. Using S1 nuclease protection analysis, a major nuclear RNA species with a 3' terminus at map unit 98.9 was detected. With the use of recombinant expression vectors and run-on transcription in isolated nuclei, we demonstrated that the Ad2 sequences from map units 97.1 to 100, inserted into either the 5' or 3' untranslated sequences of the chloramphenicol acetyltransferase gene (cat), terminated transcription in transfected cells. Termination occurred only when the 97.1- to 100-map-unit sequence was in the same direction of transcription as the major late transcript and was not observed with Ad2 sequences upstream of map unit 97.1.

Acetyltransferases↗