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W J Gehring

Publications and source records attributed to W J Gehring.

176 records · Page 10Linked to original sources

Morphologic and molecular changes in target cells during in vitro interaction with macrophages.

Recent work has indicated that macrophages can affect eukaryote cells in a variety of ways. The inhibitory or enhancing effects on target cell proliferation are mediated by soluble factors released from macrophages and appear to affect every replicating cells. Macrophages have also been shown to affect target cell viability and this destructive potential was initially considered to be tumor-specific. The present work further assesses these macrophage effects on targets by morphologic and fluorimetric methods. Morphologic analysis of the interaction between activated nonimmune macrophages (AM) and tumor cells attests to close cell-to-cell contact as an important factor in the mediation of target cell damage. All evidence suggests that damaged targets progressively disintegrate, and residues of target cell cytoplasma and/or nucleus are then engulfed as a secondary event. Analysis by impulse cytophotometry of the alterations in the DNA distribution occurring during interaction with AM revealed a marked decrease in the number of nuclei with higher DNA content. This effect was virtually identical irrespective of whether target cells were derived from normal or transformed tissues. Analysis of the consequences of AM/target cell interaction by cytofluorimetry showed that a large proportion of tumor cells lyse in the course of the interaction. However, no such killing occurred in recent explants derived from normal tissues interacted with AM; the majority of these targets were arrested in G1.

Cell Division↗

The use of 'normal' and 'transformed' gynandromorphs in mapping the primordial germ cells and the gonadal mesoderm in Drosophila.

The primordial germ cells and the gonadal mesoderm were mapped in the Drosophila embryo by analyzing the patterns of mosaicism in 'normal' and 'transformed' gynandromorphs. Relative to the adult cuticular markers the germ cells map as the posterior most structure, which coincides with their known location in the blastoderm embryo. These data support the hypothesis that the gynandromorph map reflects the real position of the primordia in the embryo. Since after the blastoderm stage the primordial germ cells migrate anteriorly these data also indicate that the map in fact corresponds to the blastoderm stage and not to a later stage of development. The genital disc maps at a single median primordium anterior and ventral to the germ cells, the gonadal mesoderm is located anterior to the genital disc and also forms a single median primordium on the ventral side of the embryo. The primordia for the genital disc and the gonadal mesoderm are unusually large in size, which presumably reflects some indeterminacy of the cell lineage leading to an 'expansion' of the map.

Animals↗

Expression of homeotic mutations in duplicated and regenerated antennae of Drosophila melanogaster.

Three homeotic mutants, aristapedia (ssa and ssa-UCl) and Nasobemia (Ns) which involve antenna-leg transformations were analyzed with respect to their time of expression. In particular we studied the question of whether these mutations are expressed when the mutant cells pass through additional cell divisions in culture. Mutant antennal discs were cultured in vivo and allowed to duplicate the antennal anlage. Furthermore, regeneration of the mutant antennal anlage was obtained by culturing eye discs and a particular fragment of the eye disc. Both duplicated and regenerated antennae showed at least a partial transformation into leg structures which indicates that the mutant gene is expressed during proliferation in culture.

Animals↗

Regulation of Antennapedia transcript distribution by the bithorax complex in Drosophila.

The homoeotic genes of Drosophila seem to be involved in the establishment of developmental pathways and the specification of different anatomical segment identities. For example, it has been proposed that a function of the Antennapedia+ (Antp+) locus is to direct embryonic cells to follow a mesothoracic developmental pathway. Using cloned cDNA probes of the Antp+ (ref. 6) locus and an improved in situ hybridization method, we found that the neural cells of the embryonic and larval mesothorax possess higher levels of Antp+ transcripts than the neural tissue of the other segments. Here we present further evidence that Antp+ products are associated with formation of the mesothorax, obtained by analysing the distribution of Antp+ transcripts in bithorax mutants. Embryos homozygous for any one of several bithorax mutations display a transformation of the epidermis of the more posterior segments into the homologous tissue of the mesothorax. For example, the metathorax and first seven abdominal segments of embryos that completely lack the bithorax gene complex show a cuticular phenotype characteristic of the normal mesothorax. By in situ hybridization of an Antp+ cDNA probe to tissue sections of these embryos, we have found that the neural cells of the transformed segments accumulate Antp+ transcripts to a level characteristic of the normal mesothorax.

Animals↗

A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes.

A repetitive DNA sequence has been identified in the Drosophila melanogaster genome that appears to be localized specifically within genes of the bithorax and Antennapedia complexes that are required for correct segmental development. Initially identified in cloned copies of the genes Antennapedia, Ultrabithorax and fushi tarazu, the sequence is also contained within two other DNA clones that have characteristics strongly suggesting that they derive from other homoeotic genes.

Animals↗

Fly and frog homoeo domains show homologies with yeast mating type regulatory proteins.

Homoeotic genes in the bithorax and Antennapedia complexes of Drosophila melanogaster appear to specify the developmental fate of segments of the fly. Some of these genes (Ultrabithorax, Antennapedia and fushi tarazu) share homology due to their conservation of a 'homoeo domain'1,2 consisting of 60 amino acids. Cross-hybridization and cloning experiments show that the homoeo domain is conserved in a frog (Xenopus laevis) gene expressed in early development and may also be present in earthworm, beetle, chicken, mouse and human genomes. The extreme conservation found in the amino acid sequences between the Drosophila and Xenopus domains suggests that the domain has a vital function in the control of early development. Here we report the results of a search made in the Dayhoff sequence bank, which reveals a lesser but apparently significant homology between the homoeo domain and the amino acids coded from parts of the a 1 and alpha 2 mating type genes of the yeast Saccharomyces cerevisiae.

Amino Acid Sequence↗

Isolation of a homoeo box-containing gene from the engrailed region of Drosophila and the spatial distribution of its transcripts.

The engrailed locus of Drosophila melanogaster has the characteristics of both a homoeotic gene and a segmentation gene: like a homoeotic gene, it specifies the development of specific compartments of the Drosophila embryo (the posterior compartments of each segment), and, like mutations of segmentation genes, lethal alleles of engrailed affect also the pattern of segmentation of the embryo. Here we report that like many of the homoeotic genes of the bithorax and Antennapedia complexes, engrailed has a 'homoeo box' sequence: also, like the segmentation gene fushi tarazu, the engrailed gene displays a periodic pattern of expression in Drosophila embryos.

Amino Acid Sequence↗

Redesigning the body plan of Drosophila by ectopic expression of the homoeotic gene Antennapedia.

Genetic and molecular studies on the expression of Antennapedia (Antp) have suggested that this gene specifies mainly the second thoracic segment. On the basis of our molecular analysis of dominant gain-of-function mutants we have postulated that the transformation of antennae into second legs is due to the ectopic overexpression of the Antp+ protein. This hypothesis was tested by inserting the complementary DNA encoding the normal Antp protein into a heat-shock expression vector and subsequent germ-line transformation. As predicted, heat induction at defined larval stages leads to the transformation of antennae into second legs. The dorsal part of the head can also be transformed into second thoracic structures (scutum) indicating that Antp indeed specifies the second thoracic segment. By ectopic overexpression of the Antp protein the body plan of the fruit fly can be altered in a predictable way.

Animals↗