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F M Hoffmann

Publications and source records attributed to F M Hoffmann.

At least 55 records · Page 3Linked to original sources
PubMed1990

Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3' cis-regulatory elements.

The pattern of structures on most of the adult cuticle of Drosophila is determined in the larval imaginal disks. The Drosophila growth factor homolog decapentaplegic (dpp) is believed to participate in pattern formation in imaginal disks, primarily along what will become the proximal-to-distal axis of adult appendages. We report that dpp expression in wing, leg, and eye-antennal imaginal disks is localized to a band of cells along the presumptive proximal-to-distal axis. The pattern and level of dpp expression in imaginal disks is affected by mutant lesions that remove 3' cis-regulatory sequences. We demonstrate that one portion of the 3' cis-regulatory region contains regulatory elements sufficient to activate gene expression in a subset of the cells that normally express dpp in the imaginal disks, allowing rescue of dpp mutant phenotypes. We propose that the complete dpp expression pattern is generated by an array of 3' regulatory elements that differ in their potency in specific disks and in certain positions within a disk. The identification of the factors that activate these elements should provide clues as to how positional information is encoded in imaginal disks.

Alcohol Dehydrogenase↗
PubMed1990

Molecular organization of the decapentaplegic gene in Drosophila melanogaster.

The decapentaplegic (dpp) locus of Drosophila melanogaster is a greater than 55 kb genetic unit required for proper pattern formation during the embryonic and imaginal development of the organism. We have proposed that these morphogenetic functions result from the action of a secreted transforming growth factor-beta (TGF-beta)-related protein product encoded by dpp. In this paper we localize 60 mutations on the molecular map of dpp. The positions of these mutations cluster according to phenotypic class, identifying the locations of specific dpp functions. By Northern and cDNA analysis, we characterize five overlapping dpp transcripts. On the basis of the locations of the overlaps relative to a previously sequenced cDNA, it is likely that these transcripts all encode similar or identical polypeptides. We propose that the bulk of dpp DNA consists of extensive arrays of cis-regulatory information. The large (greater than 25-kb) 3' cis-regulatory region represents a novel feature of dpp gene organization

Alleles↗
PubMed1990

Conservation of function of Drosophila melanogaster abl and murine v-abl proteins in transformation of mammalian cells.

The Drosophila melanogaster abl and the murine v-abl genes encode tyrosine protein kinases (TPKs) whose amino acid sequences are highly conserved. To assess functional conservation between the two gene products, we constructed Drosophila abl/v-abl-chimeric Abelson murine leukemia viruses. In these chimeric Abelson murine leukemia viruses, the TPK and carboxy-terminal regions of v-abl were replaced with the corresponding regions of D. melanogaster abl. The chimeric Abelson murine leukemia viruses were able to mediate morphological and oncogenic transformation of NIH 3T3 cells and were able to abrogate the interleukin-3 dependence of a lymphoid cell line. We also found that a virus that contained both TPK and carboxy-terminal Drosophila abl regions had no in vitro transforming activity for primary bone marrow cells and lacked the ability to induce tumors in susceptible mice. A virus that replaced only a portion of the v-abl TPK region with that of Drosophila abl had low activity in in vitro bone marrow transformation and tumorigenesis assays. These results indicate that the transforming functions of abl TPKs are only partially conserved through evolution. These results also imply that the TPK region of v-abl is a major determinant of its efficient lymphoid cell-transforming activity.

Abelson murine leukemia virus↗
PubMed1990

Biochemical characterization of the Drosophila dpp protein, a member of the transforming growth factor beta family of growth factors.

The decapentaplegic (dpp) gene of Drosophila melanogaster is required for pattern formation in the embryo and for viability of the epithelial cells in the imaginal disks. The dpp protein product predicted from the DNA sequence is similar to members of a family of growth factors that includes transforming growth factor beta (TGF-beta). We have produced polyclonal antibodies to a recombinant dpp protein made in bacteria and used a metallothionein promoter to express a dpp cDNA in Drosophila S2 cells. Similar to other proteins in the TGF-beta family, the dpp protein produced by the Drosophila cells was proteolytically cleaved, and both portions of the protein were secreted from the cells. The amino-terminal 47-kilodalton (kDa) peptide was found in the medium and in the proteins adhering to the plastic petri dish. The carboxy-terminal peptide, the region with sequence similarity to the active ligand portion of TGF-beta, was found extracellularly as a 30-kDa homodimer. Most of the 30-kDa homodimer was in the S2 cell protein adsorbed onto the surface of the plastic dish. The dpp protein could be released into solution by increased salt concentration and nonionic detergent. Under these conditions, the amino-terminal and carboxy-terminal portions of dpp were not associated in a stable complex.

Amino Acid Sequence↗
PubMed1990

Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos.

During Drosophila embryogenesis homeotic genes control the developmental diversification of body structures. The genes probably coordinate the expression of as yet unidentified target genes that carry out cell differentiation processes. At least four homeotic genes expressed in the visceral mesoderm are required for midgut morphogenesis. In addition, two growth factor homologs are expressed in specific regions of the visceral mesoderm surrounding the midgut epithelium. One of these, decapentaplegic (dpp), is a member of the transforming growth factor beta (TGF-beta) family; the other, wingless (wg), is a relative of the mammalian proto-oncogene int-1. Here we show that the spatially restricted expression of dpp in the visceral mesoderm is regulated by the homeotic genes Ubx and abd-A. Ubx is required for the expression of dpp while abd-A represses dpp. One consequence of dpp expression is the induction of labial (lab) in the underlying endoderm cells. In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells. The two growth factor genes therefore are excellent candidates for target genes that are directly regulated by the homeotic genes.

Animals↗
PubMed1990

A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis.

The decapentaplegic (dpp) gene product, a member of the transforming growth factor-beta family, is required in Drosophila embryos for normal gastrulation and the establishment of dorsal-ventral polarity in the embryo. dpp is also expressed at specific positions in the visceral mesoderm along the developing midgut. We find that mutations that eliminate the visceral mesoderm expression of dpp lead to defects in midgut morphogenesis and alter the spatially localized expression of the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Antennapedia (Antp) in the visceral mesoderm. The extracellular dpp protein migrates from the visceral mesoderm across the apposing endodermal cell layer in a region of the endoderm that expresses the homeotic gene labial (lab). Mesodermal expression of dpp is required for the expression of lab in these endodermal cells indicating that dpp mediates an inductive interaction between the two germ layers. We propose that extracellular dpp protein regulates gut morphogenesis, in part, by regulating homeotic gene expression in the visceral mesoderm and endoderm of the developing midgut.

Animals↗
PubMed1989

Drosophila abl tyrosine kinase in embryonic CNS axons: a role in axonogenesis is revealed through dosage-sensitive interactions with disabled.

During Drosophila embryogenesis, the Abelson tyrosine kinase (abl) is localized in the axons of the central nervous system (CNS). Mutations in abl have no detectable effect on the morphology of the embryonic CNS, and the mutant animals survive to the pupal and adult stages. In the absence of abl function, however, heterozygous mutations or deletions of disabled (dab) exert dominant effects, disrupting axonal organization and shifting the lethal phase of the animals to embryonic and early larval stages. Embryos that are homozygous mutant for both abl and dab fail to develop any axon bundles in the CNS, although the peripheral nervous system and the larval cuticle appear normal. The genetic interaction between these two genes begins to define a process in which both the abl tyrosine kinase and the dab gene product participate in establishing axonal connections in the embryonic CNS of Drosophila.

Animals↗
PubMed1988

DNA sequence, structure, and tyrosine kinase activity of the Drosophila melanogaster Abelson proto-oncogene homolog.

We report our molecular characterization of the Drosophila melanogaster Abelson gene (abl), a gene in which recessive loss-of-function mutations result in lethality at the pupal stage of development. This essential gene consists of 10 exons extending over 26 kilobase pairs of genomic DNA. The DNA sequence encodes a protein of 1,520 amino acids with strong sequence similarity to the human c-abl proto-oncogene beginning in the type lb 5' exon and extending through the region essential for tyrosine kinase activity. When the tyrosine kinase homologous region was expressed in Escherichia coli, phosphorylation of proteins on tyrosine residues was observed with an antiphosphotyrosine antibody. These results show that the abl gene is highly conserved through evolution and encodes a functional tyrosine protein kinase required for Drosophila development.

Amino Acid Sequence↗
PubMed1987

The Drosophila Abelson proto-oncogene homolog: identification of mutant alleles that have pleiotropic effects late in development.

The Abelson gene in Drosophila (abl) consists of ten exons extending over 26 kb of genomic DNA. The DNA sequence encodes a protein of 1520 amino acids with sequence homology to the human c-abl proto-oncogene product, beginning at the amino terminus and extending 656 amino acids through the region essential for tyrosine kinase activity. Mutant lesions in the abl gene were identified first by their failure to complement chromosomal deletions that overlap the abl DNA sequence and then by rescue of the mutant phenotypes with an abl minigene in transgenic flies. Elimination of abl zygotic function by mutations produces some recessive lethality at the pharate adult pupal stage, and mutant adults with reduced longevity, reduced fecundity, and an irregular pattern of retinal cells.

Alleles↗
PubMed1987

Identification in transgenic animals of the Drosophila decapentaplegic sequences required for embryonic dorsal pattern formation.

Mutant alleles of the Drosophila decapentaplegic (dpp) gene affect embryonic dorsal-ventral pattern formation, larval viability, and adult cuticle formation from the imaginal disks. The dpp DNA required for this array of functions spans almost 50 kb. We report that the embryonic lethal, ventralizing alleles of the dpp gene are rescued in transgenic animals by an 8-kb fragment of the wild-type dpp DNA. Full rescue, from embryonic lethality to adult viability, is obtained in two situations: in animals hemizygous for the haplolethal dpp gene, and in animals hemizygous for either of two recessive embryonic lethal alleles. In embryos null for dpp, the transformation of dorsal cuticle to ventral cuticle is blocked by one copy of the dpp transposon; two copies permit the hatching of the larvae. The portion of dpp sufficient for these embryonic functions encodes a protein with homology to the transforming growth factor-beta (TGF-beta) family of proteins (Padgett et al. 1987). The larval and imaginal disk functions of dpp are not rescued by the 8-kb portion of the gene and must require additional sequences from the 50 kb of DNA.

Animals↗
PubMed1984

The Drosophila ras oncogenes: structure and nucleotide sequence.

Three Drosophila genes homologous to the Ha-ras probe were isolated and mapped to positions 85D, 64B, and 62B on chromosome 3. Two of these genes (termed Dras 1 and Dras 2) were sequenced. In the case of Dras 1, which contains multiple introns, a cDNA clone was isolated and sequenced. In the case of Dras2, the nucleotide sequence fo the genomic clone was determined. Each gene codes for a protein with a predicted molecular weight of 21.6 kd. Alignment of the amino acid sequence of Dras 1 with the vertebrate Ha-ras protein shows that at the amino terminus and central portion (residues 1-121 and 137-164) the two proteins are remarkably similar, and have an overall homology of 75%. The Dras 2 gene lacks significant homology to the vertebrate counterpart at the extreme amino terminus and is homologous only between positions 28-120 and 139-161 (overall homology of 50%). This result suggests that the N terminus of p21 forms a distinct regulatory or functional domain. At the carboxy terminus, the major region of variability among the vertebrate ras proteins, the two Drosophila sequences also display considerable variability. However, both appear to be more similar to exon 4B of the Ki-ras gene.

Amino Acid Sequence↗
PubMed1983

Nucleotide sequences of the Drosophila src and abl homologs: conservation and variability in the src family oncogenes.

Two cloned Drosophila sequences, Dash and Dsrc, were previously isolated by hybridization to the viral oncogenes v-abl and v-src. We report that the Drosophila DNA sequences are more than 50% homologous to 700 base pairs of the vertebrate oncogenes that are essential for kinase activity of the v-abl and the v-src gene products. Alignment of the predicted amino acid sequences in the homologous regions shows amino acid sequence identities of 74% between Dash and the 5' portion of v-abl and of 54% between Dsrc and 3' portion of v-src. Comparison of the Drosophila and vertebrate sequences identifies amino acids that may be essential for the distinct functions of the c-src and the c-abl gene products and places the gene duplication event that has generated the two genes prior to the Chordate-Arthropod divergence.

Amino Acid Sequence↗
PubMed1983

Drosophila melanogaster DNA clones homologous to vertebrate oncogenes: evidence for a common ancestor to the src and abl cellular genes.

We have isolated phage clones containing the D. melanogaster sequence homologous to the v-abl oncogene, and two types of phage clones containing sequences homologous to the v-src probe. The D. melanogaster abl clone (lambda Dabl1) and one of the src clones (lambda Dsrc1) hybridize with both v-abl and v-src probes, and both map in situ to the same chromosomal position, 73B, on chromosome arm 3L. The second D. melanogaster src clone (lambda Dsrc2) does not react with the v-abl probe and hybridizes in situ to chromosomal position 64B. The hybridization pattern suggests that the src and abl cellular oncogenes have evolved from a common prototype sequence. The homologous sequences in D. melanogaster exhibit hybridization to regions in the vertebrate v-abl and v-src that are important for kinase activity and transforming potential of the viral gene products.

Animals↗
PubMed1982

Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster.

The decapentaplegic gene complex (2-4.0) in Drosophila melanogaster is defined by a series of allelic mutations affecting imaginal disk development. Decapentaplegic (dpp) mutant individuals exhibit a variety of pattern deficiencies and duplications in structures derived from one or more of the 15 major imaginal disks. Based on dpp mutant phenotypes, we suggest that the dpp gene complex is involved in the elaboration of positional information within developing epidermal tissue. The dpp mutations are recessive and fall into six phenotypic classes. Milder alleles (classes I and II) affect only one or a few disks while most alleles (classes III, IV, V and EL) affect all major imaginal disks. Class EL homozygotes are embryonic lethals; development is arrested before germ-band shortening late in gastrulation. Presently inseparable from EL, is a haplo-insufficient function (Hin-d) associated with the distal (left) end of the dpp gene complex. The dpp gene complex occupies most or all of 22F1--3, three densely staining polytene chromosome bands. A colinearity exists between map positions of the four identified functional units within the complex and the severities of mutant phenotypes caused by disruption of these functions. Most dpp mutations are gross chromosomal rearrangements; they exert polar effects on the decapentaplegic functions that are proximal to the rearrangement breakpoints in 22F. Many structural similarities exist between the decapentaplegic and bithorax gene complexes.

Alleles↗
PubMed1979

Solubilization and reconstitution of dopamine-sensitive adenylate cyclase from bovine caudate nucleus.

Dopamine-sensitive adenylate cyclase was reconstituted from the cholate-soluble components of caudate nucleus homogenate. Biological function was restored by precipitating the components from cholate and phospholipid with ammonium sulfate, dialyzing the resuspended precipitate, and activating the particulate complex with phospholipid in the assay. The reconstituted adenylate cyclase was stimulated 3- to 4-fold by dopamine and 8- to 12-fold by guanyl-5'-yl imidodiphosphate. The catecholamine stimulation was specific for dopamine and required the addition of GTP. The cholate-soluble component(s) of the basal adenylate cyclase were separated from the component(s) that conferred dopamine sensitivity by gel filtration chromatography. Dopamine-sensitive adenylate cyclase was also reconstituted from digitonin-soluble components. These were resolved into two fractions by DEAE-cellulose chromatography: one fraction contained adenylate cyclase, but both fractions were required for reconstitution of dopamine-sensitive adenylate cyclase.

Adenylyl Cyclases↗