Search PubMed⌕ Search

Biomedical subjects

E Wieschaus

Publications and source records attributed to E Wieschaus.

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

Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins.

Mutations in the Drosophila gene extradenticle (exd), a homologue of the human proto-oncogene pbx1, cause homeotic transformations by altering the morphological consequences of homeotic selector gene activity. exd has been proposed to act by contributing to the specificity of selector homeodomain proteins for their downstream targets. Here we show that exd is indeed required for the appropriate regulation of at least some of these target genes. Expression patterns of wingless, teashirt and decapentaplegic (dpp) are altered in the embryonic midgut of embryos lacking exd, while the expression of their respective regulators (abd-A, Antp and Ubx) remains normal. Co-regulation of dpp by exd and Ubx was investigated in greater detail by examining the expression of reporter constructs in exd embryos. These experiments not only define dpp regulatory regions responsive to exd, but also distinguish two functions of exd in the regulation of dpp. exd acts with Ubx to activate dpp expression in parasegment 7 (PS7), via a minimal visceral mesoderm enhancer, and exd represses dpp expression anterior to PS7. We show that even when Ubx is ubiquitously expressed at high levels in exd embryos, Ubx is incapable of activating dpp enhancer expression. Thus, exd is an indispensable component in target gene regulation by the homeotic selector proteins.

Animals↗
PubMed1994

A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation.

The folded gastrulation (fog) gene is required during Drosophila gastrulation for two morphogenetic movements, formation of the ventral furrow and invagination of the posterior midgut primordium. fog coordinates cell shape changes during these invaginations by inducing apical constriction of cells in spatially and temporally defined manners. fog is expressed in the invagination primordia in a pattern that precisely precedes the pattern of constrictions. Overexpression of fog in the dorsoanterior region of the embryo induces ectopic constrictions, indicating localization of fog transcripts may define domains of cell shape changes. fog encodes a novel protein with a putative signal sequence but no potential transmembrane domains. We suggest fog functions as a secreted signal that activates the G protein alpha subunit encoded by concertina in neighboring cells. Our analyses indicate that cell-cell communication ensures the rapid, orderly progression of constriction initiations from the middle of invagination primordia out toward the margins.

Amino Acid Sequence↗
PubMed1994

wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo.

wingless/wnt-1 signaling directs cell fate during development. Genetic analysis in Drosophila identified genes that may encode components of the wingless signal transduction system. Drosophila Armadillo, homolog of vertebrate beta-catenin, is required for wingless signaling. Unlike armadillo RNA, Armadillo protein accumulates non-uniformly in different cells of each embryonic segment. We found that cells alter their intracellular distribution of Armadillo in response to Wingless signal, accumulating increased levels of cytoplasmic Armadillo relative to those of membrane-associated protein. Levels of cytoplasmic Armadillo are also regulated by Zeste-White 3 kinase. Analysis of double mutants demonstrates that Armadillo's role in wingless signaling is direct, and that Armadillo functions downstream of both wingless and zeste-white 3. We present a model for the role of Armadillo stripes in transduction of wingless signal.

Animals↗
PubMed1994

Cell intercalation during Drosophila germband extension and its regulation by pair-rule segmentation genes.

After the onset of gastrulation, the Drosophila germband undergoes a morphological change in which its length along the anterior-posterior axis increases over two-and-a-half fold while its width along the dorsal-ventral axis simultaneously narrows. The behavior of individual cells during germband extension was investigated by epi-illumination and time-lapse video microscopy of living embryos. Cells intercalate between their dorsal and ventral neighbors during extension, increasing the number of cells along the anterior-posterior axis while decreasing the number of cells along the dorsal-ventral axis. Mutations that reduce segmental subdivision of the embryo along the anterior-posterior axis decrease both germband extension and its associated cell intercalation. In contrast, cell intercalation and germband extension are still detected in embryos that lack dorsal-ventral polarity. Characterization of germband extension and cell intercalation in mutant embryos with altered segmentation gene expression indicates that these processes are regionally autonomous and are dependent upon the establishment of striped expression patterns for certain pair-rule genes. Based on these observations, we propose a model for germband extension in which cell intercalation results from the establishment of adhesive differences between stripes of cells by pair-rule genes.

Animals↗
PubMed1993

bottleneck acts as a regulator of the microfilament network governing cellularization of the Drosophila embryo.

A dynamic network of cortical microfilaments is associated with the cleavage furrow membranes during cellularization of the Drosophila embryo. A specific set of structural rearrangements in this network is required for orchestration and execution of its mechanistic roles. We describe the characterization of the gene bottleneck (bnk), mutations in which disturb the proper sequence of rearrangements of the microfilament network, leading to a variety of morphological defects during cellularization. bnk, whose expression is restricted to the blastoderm stages of Drosophila embryogenesis, encodes a novel, exceptionally basic protein that specifically colocalizes with the microfilament network. The expression pattern and mutant phenotype of bnk suggest a direct role for this element in regulation of the dynamic restructuring of the actin-based cytoskeleton of cellularizing Drosophila embryos.

Actin Cytoskeleton↗
PubMed1993

extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1.

Mutations in the Drosophila gene extradenticle (exd) cause homeotic transformations by altering the morphological consequences of homeotic selector gene activity. We have cloned and sequenced exd: it encodes a homeodomain protein with extensive identity (71%) to the human proto-oncoprotein Pbx1. exd is expressed during embryogenesis when the selector homeodomain proteins of the Antennapedia and bithorax complexes establish segmental identity. Maternally expressed exd is uniform and can suppress the segmental transformations of embryos lacking zygotic exd. While zygotic exd expression is also at first uniform, later expression is modulated by the homeotic selector genes. These studies support the view that exd acts with the selector homeodomain proteins as a DNA-binding transcription factor, thereby altering their regulation of downstream target genes.

Amino Acid Sequence↗
PubMed1993

The product of the Drosophila melanogaster segment polarity gene armadillo is highly conserved in sequence and expression in the housefly Musca domestica.

Segmental pattern in Drosophila melanogaster is set up via a set of cell-cell interactions mediated by the products of the segment polarity genes. Among these is the armadillo gene, whose product seems to be required for the reception of an intercellular signal encoded by the wingless gene. As part of our effort to relate the structure of the armadillo protein to its function within the cell, we have examined the evolutionary conservation of the armadillo gene during insect evolution. We have cloned the armadillo gene from the housefly, Musca domestica, which diverged from Drosophila 100 million years ago. The Musca protein is 97.5% identical to that in Drosophila, while the noncoding sequences have diverged extensively. This remarkable degree of conservation at the protein level is mirrored in the expression pattern of the armadillo protein. Antibodies against the Drosophila protein cross-react with a Musca protein of the appropriate size. We have also used these antibodies to show that the Musca armadillo protein has a pattern of expression in larval and adult tissues similar to that of Drosophila armadillo. We discuss the implications of conservation of structure and expression for the cellular role of the armadillo protein and its mammalian homologs.

Amino Acid Sequence↗
PubMed1993

A role for the Drosophila segment polarity gene armadillo in cell adhesion and cytoskeletal integrity during oogenesis.

The epithelial sheet is a structural unit common to many tissues. Its organization appears to depend on the function of the multi-protein complexes that form adherens junctions. Elegant cell biological experiments have provided support for hypotheses explaining the function of adherens junctions and of their components. These systems, however, lack the ability to test function within an entire organism during development. The realization that the product of the Drosophila segment polarity gene armadillo is related to the vertebrate adhesive junction components plakoglobin and beta-catenin led to the suggestion that armadillo might provide a genetic handle to study adhesive junction structure and function. An examination of the potential function of Armadillo in cell-cell adhesive junctions was initiated using the Drosophila ovary as the model system. We examined the distribution of Armadillo in the Drosophila ovary and demonstrated that this localization often parallels the location of cell-cell adhesive junctions. The consequences of removing armadillo function from the germ-line cells of the ovary were also examined. Germ-line armadillo mutations appear to disrupt processes requiring cell adhesion and integrity of the actin cytoskeleton, consistent with a role for Armadillo in cell-cell adhesive junctions. We have also used armadillo mutations to examine the effects on ovarian development of altering the stereotyped cell arrangements of the ovary. The implications of these results for the role of adhesive junctions during development are discussed.

Animals↗
PubMed1993

Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos.

Each segment of a Drosophila larva shows a precisely organized pattern of cuticular structures, indicating diverse cellular identities in the underlying epidermis. Mutations in the segment polarity genes alter the cuticle pattern secreted by the epidermal cells; these mutant patterns provide clues about the role that each gene product plays in the development of wild-type epidermal pattern. We have analyzed embryos that are multiply mutant for five key patterning genes: wingless, patched, engrailed, naked and hedgehog. Our results indicate that wild-type activity of these five segment polarity genes can account for most of the ventral pattern elements and that their gene products interact extensively to specify the diverse cellular identities within the epidermis. Two pattern elements can be correlated with individual gene action: wingless is required for formation of naked cuticle and engrailed is required for formation of the first row of denticles in each abdominal denticle belt. The remaining cell types can be produced by different combinations of the five gene activities. wingless activity generates the diversity of cell types within the segment, but each specific cell identity depends on the activity of patched, engrailed, naked and hedgehog. These molecules modulate the distribution and interpretation of wingless signalling activity in the ventral epidermal cells and, in addition, each can contribute to pattern through a pathway independent of the wingless signalling pathway.

Animals↗
PubMed1992

The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.

Three proteins identified by quite different criteria in three different systems, the Drosophila segment polarity gene armadillo, the human desmosomal protein plakoglobin, and the Xenopus E-cadherin-associated protein beta-catenin, share amino acid sequence similarity. These findings raise questions about the relationship among the three molecules and their roles in different cell-cell adhesive junctions. We have found that antibodies against the Drosophila segment polarity gene armadillo cross react with a conserved vertebrate protein. This protein is membrane associated, probably via its interaction with a cadherin-like molecule. This cross-reacting protein is the cadherin-associated protein beta-catenin. Using anti-armadillo and antiplakoglobin antibodies, it was shown that beta-catenin and plakoglobin are distinct molecules, which can coexist in the same cell type. Plakoglobin interacts with the desmosomal glycoprotein desmoglein I, and weakly with E-cadherin. Although beta-catenin interacts tightly with E-cadherin, it does not seem to be associated with either desmoglein I or with isolated desmosomes. Anti-armadillo antibodies have been further used to determine the intracellular localization of beta-catenin, and to examine its tissue distribution. The implications of these results for the structure and function of different cell-cell adhesive junctions are discussed.

Amino Acid Sequence↗
PubMed1992

The Drosophila cellularization gene nullo produces a blastoderm-specific transcript whose levels respond to the nucleocytoplasmic ratio.

The initial development of the Drosophila embryo is characterized by rapid nuclear mitosis without cytokinesis. After 13 such mitoses, a coordinated cell division process called cellularization occurs, during which membranes simultaneously enclose each nucleus in a cell. Cellularization requires the establishment of a hexagonal network of actin and myosin filaments in the cortex of the embryo; the filaments are located on the cytoplasmic face of the invaginating membrane furrows. Zygotic expression of the nullo gene is essential for the maintenance of an intact actin-myosin network. We have cloned the nullo gene and present its sequence as well as a characterization of nullo transcript levels in wild-type and mutant embryos. The nullo gene encodes a predicted protein of 213 amino acids, a large proportion of which is basic. nullo transcripts are first detectable at nuclear cell cycle 11, peak in accumulation at the end of cycle 13, and disappear rapidly as cellularization begins. The gene does not appear to be expressed at any other time in the life of the organism. The normal accumulation of nullo transcripts does not require gene activity of other zygotic cellularization genes. The regulation of nullo RNA levels during cycle 14, however, is coupled to the nucleocytoplasmic ratio, which also controls the cessation of rapid, synchronous mitosis just before cellularization.

Amino Acid Sequence↗
PubMed1992

orthodenticle activity is required for the development of medial structures in the larval and adult epidermis of Drosophila.

Lethal alleles of orthodenticle (= otd) cause abnormalities in the embryonic head that reflect an early role in anterior pattern formation. In addition, otd activity is required for the development of the larval and adult epidermis. Clonal analysis of both viable and lethal alleles shows that the adult requirement for otd is restricted to medial regions of certain discs. When otd activity is reduced or removed, some medial precursor cells produce bristles and cuticle characteristic of more lateral structures. Similar medial defects are observed in the larval epidermis of embryos homozygous for lethal otd alleles. Antibodies to otd recognize a nuclear protein found at high levels in the medial region of the eye antennal discs, the leg discs, the genital discs and along the ventral midline of the ventral epidermis of the embryo. These results suggest that the otd gene product is required to specify medial cell fates in both the larval and adult epidermis.

Animals↗
PubMed1991

The Drosophila gastrulation gene concertina encodes a G alpha-like protein.

Gastrulation is a complex process requiring the coordination of cell shape changes and cell movements. In Drosophila, gastrulation begins immediately upon cellularization of the blastoderm stage embryo with the formation of the ventral furrow and posterior midgut. Cells that form both of these invaginations change their shape via apical constriction. Embryos from mothers homozygous for mutations in the concertina (cta) gene begin furrow formation by forming a zone of tightly apposed cells, constrict some cells, and then fail to constrict enough cells to form an organized groove. The cta gene has been cloned, and sequence analysis suggests that it encodes an alpha subunit of a G protein. G proteins have a role in cell-cell communication as mediators of signals between membrane-bound receptors and intracellular effectors. The phenotype of embryos from homozygous cta mothers suggests that the cta gene plays a role in a signal transduction pathway used during gastrulation.

Amino Acid Sequence↗
PubMed1991

Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology.

In mutagenesis screens for recessive female sterile mutations on the second chromosome of Drosophila melanogaster 528 lines were isolated which allow the homozygous females to survive but cause sterility. In 62 of these lines early stages of oogenesis are affected, and these females usually do not lay any eggs. In 333 lines oogenesis proceeds apparently normally to stage 8 of oogenesis, but morphological defects become often apparent during later stages of oogenesis, and are visible in the defective eggs produced by these females whereas 133 lay eggs that appear morphologically normal, but do not support normal embryonic development. Of the lines 341 have been genetically characterized and define a total of 140 loci on the second chromosome. Not all the loci are specific for oogenesis. From the numbers obtained we estimate that the second chromosome of Drosophila contains about 13 loci that are relatively specific for early oogenesis, 70 loci that are specifically required in mid to late oogenesis, and around 30 maternal-effect lethals.

Animals↗
PubMed1991

The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation.

The segment polarity genes of Drosophila were initially defined as genes required for pattern formation within each embryonic segment. Some of these genes also function to establish the pattern of the adult cuticle. We have examined the role of the armadillo (arm) gene in this latter process. We confirmed and extended earlier findings that arm and the segment polarity gene wingless are very similar in their effects on embryonic development. We next discuss the role of arm in pattern formation in the imaginal discs, as determined by using a pupal lethal allele, by analyzing clones of arm mutant tissue in imaginal discs, and by using a transposon carrying arm to produce adults with a reduced level of arm. Together, these experiments established that arm is required for the development of all imaginal discs. The requirement for arm varies along the dorsal-ventral and proximal-distal axes. Cells that require the highest levels of arm are those that express the wingless gene. Further, animals with reduced arm levels have phenotypes that resemble those of weak alleles of wingless. We present a description of the patterns of arm protein accumulation in imaginal discs. Finally, we discuss the implications of these results for the role of arm and wingless in pattern formation.

Animals↗
PubMed1991

Gastrulation in Drosophila: the formation of the ventral furrow and posterior midgut invaginations.

The ventral furrow and posterior midgut invaginations bring mesodermal and endodermal precursor cells into the interior of the Drosophila embryo during gastrulation. Both invaginations proceed through a similar sequence of rapid cell shape changes, which include apical flattening, constriction of the apical diameter, cell elongation and subsequent shortening. Based on the time course of apical constriction in the ventral furrow and posterior midgut, we identify two phases in this process: first, a slow stochastic phase in which some individual cells begin to constrict and, second, a rapid phase in which the remaining unconstricted cells constrict. Mutations in the concertina or folded gastrulation genes appear to block the transition to the second phase in both the ventral furrow and the posterior midgut invaginations.

Animals↗