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F M Hoffmann

Publications and source records attributed to F M Hoffmann.

At least 37 records · Page 2Linked to original sources
PubMed1994

Embryonic expression patterns of the Drosophila decapentaplegic gene: separate regulatory elements control blastoderm expression and lateral ectodermal expression.

Patterns of decapentaplegic (dpp) transcripts derived from the intact gene were compared to the patterns of transcripts generated by partial dpp transgenes in Drosophila embryos. Sequences closest to the dpp coding regions, the dpp hin region, were sufficient to express lacZ-tagged mRNA in patterns indistinguishable from the patterns of endogenous dpp expression in the dorsal and terminal cells at the blastoderm stage, in the dorsal ectoderm during germ band elongation, and in narrow stripes of ectodermal cells along the dorsal edge of the ectoderm and at the boundary between the lateral and ventral neurogenic regions during germ band shortening. The latter pattern of expression responded to the segment polarity genes naked and wingless. However, these dpp sequences were not sufficient to drive lacZ-tagged mRNA expression in other cells normally expressing dpp, including cells in the gnathal segments, the clypeolabrum, the foregut, the midgut visceral mesoderm, and the hindgut. Two separate regulatory regions were found in the dpp hin region. A 479 bp region upstream of the promoter was necessary for the segmented pattern of expression in the lateral ectoderm and for expression in the midgut endoderm. Cis-acting elements in the 2 kbp second intron directed expression in the dorsal and terminal regions of the blastoderm, acted on a heterologous promoter, the P-element promoter, and responded to pattern information derived from the maternal effect dorsal/ventral patterning genes.

Animals↗
PubMed1994

Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp, and wingless, causing specific morphological defects.

The patterns of homeotic gene expression in the Drosophila midgut visceral mesoderm are instrumental in several morphogenetic events, including the formation of the gastric caeca and the positioning of the three midgut constrictions. We demonstrate that a potent regulator of homeotic gene expression in the visceral mesoderm is the secreted growth factor-like molecule encoded by the decapentaplegic (dpp) gene. Ectopic dpp in the visceral mesoderm caused changes in the gene expression of Sex combs reduced, Antennapedia, Ultrabithorax (Ubx), and abdominal-A (abd-A) and disrupted the formation of the gastric caeca and the first and third midgut constrictions. Ectopic dpp also induced expression of teashirt, wingless (wg) and the endogenous dpp gene in the visceral mesoderm and enhanced labial expression in the adjacent endoderm. The patterns of gene expression and the formation of the second midgut constriction in the presence of ectopic dpp are most consistent with a dpp-induced transformation of virtually the entire midgut to cell fates normally seen only in the parasegment (ps)7 and ps8 regions of the midgut. We conclude that dpp is a primary signal in maintaining Ubx expression in the visceral mesoderm in a pattern different from Ubx expression in the embryonic ectoderm and in providing a cell-cell communication mechanism by which Ubx expression influences gene expression across germlayers and across the ps7 to ps8 parasegment boundary in the visceral mesoderm.

Animals↗
PubMed1994

Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A.

Reported assays of the bone morphogenetic proteins (BMPs) have not in general revealed specific functions for the different proteins, belying the specificity implied by the evolutionary conservation and distinct expression patterns of the genes encoding BMPs. We have used assays of developmental function to show that the two Drosophila homologues of the BMPs, decapentaplegic (dpp) and 60A, that both induce ectopic bone formation in mammalian assay systems, have distinct effects in Drosophila development. A binary expression system using the yeast transcriptional activator GAL4 directed identical patterns of tissue and temporally specific dpp and 60A expression. When dpp enhancer elements drove GAL4 expression, GAL4-responsive dpp transgenes rescued dpp mutant phenotypes, but GAL4-responsive 60A transgenes did not. Ectopic ectodermal expression of dpp during gastrulation respecified the dorsal/ventral pattern of the embryo. In contrast, ectopic 60A expression had no detectable effects on embryonic development but led to defects in adult structures or lethality during metamorphosis. Expression of 60A in cells expressing dpp did not interfere with dpp functions, indicating that dysfunctional heterodimers did not form at sufficient levels to inhibit dpp. These specific developmental responses in Drosophila indicate that in vivo functions of BMP-like factors can be more specific than indicated by the ectopic bone formation assays and that the Drosophila embryo provides an assay system sensitive to the structural differences that contribute to BMP specificity in vivo.

Amino Acid Sequence↗
PubMed1993

Drosophila transforming growth factor beta superfamily proteins induce endochondral bone formation in mammals.

Both decapentaplegic (dpp) protein and 60A protein have been implicated in pattern formation during Drosophila melanogaster embryogenesis. Within the C-terminal domain, dpp and 60A are similar to human bone morphogenetic protein 2 (75% identity) and human osteogenic protein 1 (70% identity), respectively. Both recombinant human bone morphogenetic protein 2 and recombinant human osteogenic protein 1 have been shown to induce bone formation in vivo and to restore large diaphyseal segmental defects in various animal models. We examined whether the Drosophila proteins, dpp and 60A, have the capacity to induce bone formation in mammals by using the rat subcutaneous bone induction model. Highly purified recombinant dpp and 60A induced the formation of cartilage, bone, and bone marrow in mammals, as determined by histological observations and by measurements of the specific activity of alkaline phosphatase and calcium content of the implants, thereby demonstrating that related proteins from phylogenetically distant species are capable of inducing bone formation in mammals when placed in sites where progenitor cells are available.

Amino Acid Sequence↗
PubMed1993

Identification of two regions from the Drosophila decapentaplegic gene required for embryonic midgut development and larval viability.

The Drosophila decapentaplegic (dpp) gene, a member of the transforming growth factor-beta family, is required for dorsal/ventral pattern formation and midgut and imaginal disk development. We have identified a 3-kb upstream regulatory region necessary for dpp expression in the visceral mesoderm of the gastric caeca primordia and a second 2.5-kb upstream regulatory region necessary for dpp expression in the midgut visceral mesoderm corresponding to a portion of abdominal segments 1 and 2 (parasegment 7). These regulatory regions act over a distance of up to 10-kb on all four of the dpp promoters examined. Absence of dpp expression in the gastric caeca primordia caused defective development of the gastric caeca and a concomitant partial reduction in larval and pupal viability. Absence of dpp expression in the visceral mesoderm of parasegment 7 caused a reduction in the length of the central portion of the larval gut and a change in the morphology of the midgut cells in this region but had little effect on the survival of the animals to the adult stage. However, a larval lethal phenotype was observed when both the central portion of the larval midgut and the gastric caeca were defective.

Animals↗
PubMed1993

Dosage-sensitive modifiers of Drosophila abl tyrosine kinase function: prospero, a regulator of axonal outgrowth, and disabled, a novel tyrosine kinase substrate.

In the absence of the Drosophila abl protein-tyrosine kinase (PTK), loss-of-function mutations in either disabled or prospero have dominant phenotypic effects on embryonic development. Molecular and genetic characterizations indicate that the products of these genes interact with the abl PTK by different mechanisms. The interaction between abl and prospero, which encodes a nuclear protein required for correct axonal outgrowth, is likely to be indirect. In contrast, the product of disabled may be a substrate for the abl PTK. The disabled protein is colocalized with abl in axons, its predicted amino acid sequence contains 10 motifs similar to the major autophosphorylation site of abl, and the protein is recognized by antibodies to phosphotyrosine.

Amino Acid Sequence↗
PubMed1992

TGF-beta family factors in Drosophila morphogenesis.

Many Drosophila genes have now been identified with substantial sequence similarity to vertebrate protooncogenes and growth factors. Some of these have been isolated directly by cross-hybridization with vertebrate probes and some have been recognized in the sequences of genes cloned because of their intiguing mutant phenotypes. An example of a gene isolated for its interesting development functions but with homology to a vertebrate growth factor is the Drosophila decapentaplegic gene (dpp). An example of a Drosophila gene isolated by virtue of its sequence conservation is the vgr/60A gene. Both dpp and vgr/60A are members of the transforming growth factor-beta family and are most similar to the human bone morphogenetic proteins. The regulation of the dpp gene by several different groups of pattern formation genes including the dorsal/ventral group, the terminal group, the segment polarity genes, and the homeotic genes indicates that many events in embryogenesis require the cell to cell communication mediated by the secreted dpp protein. The temporal and spatial pattern of vgr/60A expression differs from that of dpp indicating that it may be regulated by different pattern information genes. The experimental advantages of the Drosophila system should permit a better understanding of the importance of growth factor homologs in specific developmental events, aid in establishing the functional interactions between these regulatory molecules, and identify new genes that are important for the biological functions of growth factors. It is likely that some of the newly identified genes will have vertebrate homologs and the analysis of these may be helpful in studies on vertebrate development and tumor biology.

Animals↗
PubMed1992

Sequence, biochemical characterization, and developmental expression of a new member of the TGF-beta superfamily in Drosophila melanogaster.

More than 20 members of the transforming growth factor-beta (TGF-beta) superfamily of growth and differentiation factors have been implicated in development. One member of the TGF-beta family has been previously reported from Drosophila, the decapentaplegic (dpp) gene which is involved in embryonic dorsal/ventral polarity, embryonic gut formation, and imaginal disk development. Using PCR methods, we have identified a second Drosophila gene in the TGF-beta family. It encodes a protein product that is more similar to the TGF-beta-related human bone morphogenetic proteins (BMPs) 5, 6, and 7 than it is to the Drosophila dpp gene product. Because of its localization on the polytene chromosome map, we refer to this gene as 60A. Expression of a 60A cDNA in Drosophila S2 cells was used to determine that 60A encodes a preproprotein that is processed to yield secreted amino- and carboxy-terminal polypeptides. The carboxy-terminal peptides are recovered as disulfide-linked homodimers. The 60A transcripts and protein are first detected at the onset of gastrulation, primarily in the mesoderm of the extending germ band. As the germ band retracts, and throughout later stages of embryonic development, the 60A transcript and protein are most readily detected in cells of the developing foregut and hindgut.

Amino Acid Sequence↗
PubMed1992

Learning about cancer genes through invertebrate genetics.

Genetic studies in yeast, nematodes and Drosophila are revealing the signal transduction pathways that regulate differentiation and cell proliferation. Some of the critical molecules involved are homologous to proto-oncogenes and others are likely to be analogous to the products of tumor suppressor genes.

Animals↗
PubMed1992

Increased levels of the Drosophila Abelson tyrosine kinase in nerves and muscles: subcellular localization and mutant phenotypes imply a role in cell-cell interactions.

Mutations in the Drosophila Abelson tyrosine kinase have pleiotropic effects late in development that lead to pupal lethality or adults with a reduced life span, reduced fecundity and rough eyes. We have examined the expression of the abl protein throughout embryonic and pupal development and analyzed mutant phenotypes in some of the tissues expressing abl. abl protein, present in all cells of the early embryo as the product of maternally contributed mRNA, transiently localizes to the region below the plasma membrane cleavage furrows as cellularization initiates. The function of this expression is not yet known. Zygotic expression of abl is first detected in the post-mitotic cells of the developing muscles and nervous system midway through embryogenesis. In later larval and pupal stages, abl protein levels are also highest in differentiating muscle and neural tissue including the photoreceptor cells of the eye. abl protein is localized subcellularly to the axons of the central nervous system, the embryonic somatic muscle attachment sites and the apical cell junctions of the imaginal disk epithelium. Evidence for abl function was obtained by analysis of mutant phenotypes in the embryonic somatic muscles and the eye imaginal disk. The expression patterns and mutant phenotypes indicate a role for abl in establishing and maintaining cell-cell interactions.

Animals↗
PubMed1991

Transforming growth factor-beta-related genes in Drosophila and vertebrate development.

The Drosophila decapentaplegic gene, the Xenopus activin genes and the genes encoding the mouse bone morphogenetic proteins are transforming growth factor-beta-related genes whose roles in development are the focus of current studies. They exhibit elaborate patterns of expression during development, and the protein products have potent effects on the differentiation of specific cell types.

Activins↗
PubMed1991

Identification of a fibroblast growth factor-binding protein in Drosophila melanogaster.

As assessed by competitive binding and protein-crosslinking experiments, Drosophila melanogaster cells possess basic fibroblast growth factor (bFGF)-specific binding proteins that are similar to FGF receptors on vertebrate cells in molecular weight and binding affinity; these D. melanogaster cells, however, have no detectable binding proteins for acidic fibroblast growth factor (aFGF). Consistent with the presence of bFGF-specific binding proteins, D. melanogaster cells degrade bFGF but not aFGF. These results indicate the conservation of heparin-binding growth factors and receptors between vertebrates and D. melanogaster.

Animals↗
PubMed1990

Genetic suppression of mutations in the Drosophila abl proto-oncogene homolog.

The Drosophila abelson (abl) gene encodes the homolog of the mammalian c-abl cytoplasmic tyrosine kinase and is an essential gene for the development of viable adult flies. Three second-site mutations that suppress the lethality caused by the absence of abl function have been isolated, and all three map to the gene enabled (ena). The mutations are recessive embryonic lethal mutations but act as dominant mutations to compensate for the neural defects of abl mutants. Thus, mutations in a specific gene can compensate for the absence of a tyrosine kinase.

Animals↗
PubMed1990

Genetic analysis of a Drosophila neural cell adhesion molecule: interaction of fasciclin I and Abelson tyrosine kinase mutations.

Drosophila fasciclin I is a homophilic cell adhesion molecule expressed in the developing embryo on the surface of a subset of fasciculating CNS axons, all PNS axons, and some nonneuronal cells. We have identified protein-null mutations in the fasciclin I (fas I) gene, and show that these mutants are viable and do not display gross defects in nervous system morphogenesis. The Drosophila Abelson (abl) proto-oncogene homolog encodes a cytoplasmic tyrosine kinase that is expressed during embryogenesis primarily in developing CNS axons; abl mutants show no gross defects in CNS morphogenesis. However, embryos doubly mutant for fas I and abl display major defects in CNS axon pathways, particularly in the commissural tracts where expression of these two proteins normally overlaps. The double mutant shows a clear defect in growth cone guidance; for example, the RP1 growth cone (normally fas I positive) does not follow its normal path across the commissure.

Alleles↗
PubMed1990

Homologs of vertebrate growth factors in Drosophila melanogaster and other invertebrates.

The molecular characterization of a number of loci that control developmental processes in invertebrates has revealed that a subset of these genes encode products that are homologous to vertebrate growth factors. Genetic analyses of the autonomy of action and molecular analysis of the patterns of expression of these genes have demonstrated that products of some of these loci (e.g., the EGF homologs, Notch, Delta, lin-12, and glp-1) appear to act in a cell-autonomous manner, while the products of other such loci (e.g., the TGF-beta homolog decapentaplegic and the murine int-1 homolog wingless) act in a nonautonomous manner. Studies of a number of invertebrate EGF homologs, including Notch, Delta, lin-12, and glp-1, for which we are beginning to achieve some reasonable understanding, reveal three common themes. First, each of these loci had been implicated in the determination of cell fates. The products of these loci appear to act at the level of single cells (i.e., they are required for the local choice between alternative determined states). The action of each of these loci within the context of determinative processes is clearly pleiotropic; mutations in each of these genes are correlated with multiple developmental defects. Second, the preponderance of evidence indicates that products of each of these loci function in a cell-autonomous manner during development. This shared character implies that these loci do not encode precursors of EGF-like molecules that act, in turn, as diffusible effectors in determinative decisions. It appears, rather, that these molecules function in association with the membranes of the cells in which they are produced and may constitute components of a class of receptors required for sensing diverse cues that specify particular cell fates during development. Third, we propose that EGF-like sequences found within each of these products function as protein-protein contact motifs that are essential for intermolecular interactions that involve membrane-bound molecules and are central to determinative decisions during development. Assignment of such a function to these sequences is consistent with recent findings indicating that EGF-homologous sequences found in urokinase (Apella et al., 1987) and blood coagulation factor IX (Rees et al., 1988) constitute sites that are required for binding to appropriate interacting proteins and are distinct from the respective "active" sites of each molecule. Within the context of this proposal, products of the EGF-homologous invertebrate genes noted above would participate in the transfer of information required for the specification of cell fate from the extracellular compartment to the cell interior.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

Cytogenetic analysis of chromosome region 73AD of Drosophila melanogaster.

The 73AD salivary chromosome region of Drosophila melanogaster was subjected to mutational analysis in order to (1) generate a collection of chromosome breakpoints that would allow a correlation between the genetic, cytological and molecular maps of the region and (2) define the number and gross organization of complementation groups within this interval. Eighteen complementation groups were defined and mapped to the 73A2-73B7 region, which is comprised of 17 polytene bands. These complementation groups include the previously known scarlet (st), transformer (tra) and Dominant temperature-sensitive lethal-5 (DTS-5) genes, as well as 13 new recessive lethal complementation groups and one male and female sterile locus. One of the newly identified lethal complementation groups corresponds to the molecularly identified abl locus, and another gene is defined by mutant alleles that exhibit an interaction with the abl mutants. We also recovered several mutations in the 73C1-D1.2 interval, representing two lethal complementation groups, one new visible mutant, plucked (plk), and a previously known visible, dark body (db). There is no evidence of a complex of sex determination genes in the region near tra.

Animals↗