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M Leptin

Publications and source records attributed to M Leptin.

At least 19 recordsLinked to original sources
PubMed2000

Fibroblast growth factor receptor-dependent morphogenesis of the Drosophila mesoderm.

The Drosophila fibroblast growth factor (FGF) receptors Heartless and Breathless are required for the morphogenesis of the mesoderm and the tracheal system. In this article we discuss a number of questions relating to the morphogenesis of these tissues and speculate on poorly understood aspects of the underlying mechanisms. As yet a ligand has not been identified for Heartless, but in the case of Breathless the ligand may in some situations act as a chemotactic signal. We consider it unlikely that release of a distant chemotactic signal plays a role in the morphogenesis of the mesoderm. Instead we propose that the change in the mesoderm from an invaginated epithelium to a single layer of cells spread out on the ectoderm could be a result of the mesodermal cells trying to maximize their contact with the ectoderm. Exactly how the activation of the FGF receptors affects cell behaviour and leads to cell movement is not understood. The signal could simply be permissive, causing cells to become motile, or it could act as a directional signal for cells that are already motile, or perhaps provide both functions. Furthermore, it is unclear how signal transduction is coupled to morphological change. It seems unlikely that activation of transcription targets is essential for cell migration and it is possible that FGF signalling may have a direct effect on the cytoskeleton independent of the activation of the mitogen-activated protein kinase cascade. Analysis of the function of dof, which encodes a cytoplasmic protein required for FGF signal transduction may provide an insight into these issues.

Animals↗
PubMed2000

Tribbles, a cell-cycle brake that coordinates proliferation and morphogenesis during Drosophila gastrulation.

BACKGROUND: The final shape and size of an organism is determined by both morphogenetic processes and cell proliferation and it is essential that these processes be properly coordinated. In particular, cell division is incompatible with certain types of morphogenetic cell behaviour, such as migration, adhesion and changes in cell shape. Mechanisms must therefore exist to ensure that one does not interfere with the other. RESULTS: We address here the coordination of proliferation and morphogenesis during the development of the mesoderm in Drosophila. We show that it is essential that mitosis be blocked in the mesoderm during early gastrulation, and identify the putative serine/threonine kinase Tribbles as controlling this block. In its absence, the mitotic block is lifted, resulting in severe defects during early gastrulation. Tribbles, a homologue of a group of vertebrate proteins of unknown function, acts in concert with another, as yet unidentified, factor to counteract the activity of the protein phosphatase Cdc25/String. CONCLUSIONS: In a finely tuned balance with Cdc25/String, Tribbles controls the timing of mitosis in the prospective mesoderm, allowing cell-shape changes to be completed. This mechanism for coordinating cell division and cell-shape changes may have helped Drosophila to evolve its mode of rapid early development.

Amino Acid Sequence↗
PubMed2000

Cell movements during gastrulation: come in and be induced.

The conversion of an epithelial monolayer into a multilayered structure consisting of the three germ layers, ectoderm, mesoderm and endoderm, constitutes a conserved theme in the early development of animals. This is accomplished by morphogenetic movements that occur during gastrulation and serve not only to generate shape but also to ensure that cells receive the right signals at the right time. Recent evidence of the role of molecular interactions facilitated by cell movements in continuously defining the chick 'organizer' during gastrulation challenges the notion that it is a fixed cell population derived from an exclusive cell lineage.

Animals↗
PubMed1999

Developmental and cell biological functions of the Drosophila DEAD-box protein abstrakt.

BACKGROUND: DEAD-box proteins are a large family of proteins found in bacteria, plants and animals, but only few have been analysed functionally. They are involved in the regulation of various aspects of RNA processing and metabolism, including splicing, transport and translation. The study of their function in multicellular organisms has been restricted to a few special cases, such as the Vasa protein in the fruit fly Drosophila. RESULTS: We show that abstrakt, a gene originally identified genetically by its effect on axon outgrowth and fasciculation of the Bolwig nerve, encodes a new Drosophila DEAD-box protein of which the closest homologue is a human gene of unknown function. Using temperature-sensitive alleles to assay its function, we found that abstrakt is essential for survival at all stages throughout the life cycle of the fly. Mutants show specific defects in many developmental processes, including cell-shape changes, localisation of RNA and apoptosis. CONCLUSIONS: Abstrakt is not globally required for RNA splicing, transport, subcellular localisation or translation. Nevertheless, there is a widespread requirement for Abstrakt during post-transcriptional gene expression. Abstrakt must affect processing of specific subsets of RNAs, suggesting that differential post-translational control during development is more common than previously suspected.

Amino Acid Sequence↗
PubMed1999

Gastrulation in Drosophila: the logic and the cellular mechanisms.

The egg contains a set of molecules that can be used to trigger cell-shape changes leading to morphogenetic movements. The temporally and spatially controlled activation of these molecules, and hence the choreography of gastrulation movements, is determined by region-specific expression of transcription factors which turn on a set of downstream targets whose products mediate the successive steps of gastrulation.

Animals↗
PubMed1998

The Drosophila protein Dof is specifically required for FGF signaling.

Receptor tyrosine kinases (RTKs) transmit signals to the cell nucleus via the MAP kinase (MAPK) cascade, using specific molecules to link the activated receptors to the MAPK cascade activator, Ras. We have identified a component of the FGF receptor (FGFR) signal transduction pathway, Downstream of FGFR (Dof). Dof is an intracellular protein that is essential for signal transmission by the FGFR and acts downstream of the receptor and upstream of Ras. Unlike other signaling molecules that act downstream of RTKs, Dof is not expressed ubiquitously but is present exclusively in cells that express FGFRs. Dof is needed in these cells for activation of the MAPK cascade via FGF signaling, but not for activation via other RTK ligands. Dof therefore appears to be committed exclusively to FGFR-mediated signal transduction.

Amino Acid Sequence↗
PubMed1998

The genetic control of the distinction between fat body and gonadal mesoderm in Drosophila.

The somatic muscles, the heart, the fat body, the somatic part of the gonad and most of the visceral muscles are derived from a series of segmentally repeated primordia in the Drosophila mesoderm. This work describes the early development of the fat body and its relationship to the gonadal mesoderm, as well as the genetic control of the development of these tissues. Segmentation and dorsoventral patterning genes define three regions in each parasegment in which fat body precursors can develop. Fat body progenitors in these regions are specified by different genetic pathways. Two regions require engrailed and hedgehog for their development while the third is controlled by wingless. decapentaplegic and one or more unknown genes determine the dorsoventral extent of these regions. In each of parasegments 10-12 one of these regions generates somatic gonadal precursors instead of fat body. The balance between fat body and somatic gonadal fate in these serially homologous cell clusters is controlled by at least five genes. We suggest a model in which tinman, engrailed and wingless are necessary to permit somatic gonadal develoment, while serpent counteracts the effects of these genes and promotes fat body development. The homeotic gene abdominalA limits the region of serpent activity by interfering in a mutually repressive feed back loop between gonadal and fat body development.

Animals↗
PubMed1997

The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation.

The Rho GTPases mediate actin rearrangements that are likely to be required for the numerous cell shape changes in a developing embryo. In a genetic screen for Rho signaling pathway components in Drosophila, we identified a gene, DRhoGEF2, that encodes a predicted Rho-specific guanine nucleotide exchange factor. Embryos lacking DRhoGEF2 fail to gastrulate due to a defect in cell shape changes required for tissue invagination, and expression of a dominant-negative Rho GTPase in early embryos results in similar defects. Evidence is also presented that DRhoGEF2 mediates these specific cell shape changes in response to the extracellular ligand, Fog. Together, these results establish a Rho-mediated signaling pathway that is essential for the major morphogenetic events in Drosophila gastrulation.

Amino Acid Sequence↗
PubMed1997

Control of cell fates and segmentation in the Drosophila mesoderm.

The primordia for heart, fat body, and visceral and somatic muscles arise in specific areas of each segment in the Drosophila mesoderm. We show that the primordium of the somatic muscles, which expresses high levels of twist, a crucial factor of somatic muscle determination, is lost in sloppy-paired mutants. Simultaneously, the primordium of the visceral muscles is expanded. The visceral muscle and fat body primordia require even-skipped for their development and the mesoderm is thought to be unsegmented in even-skipped mutants. However, we find that even-skipped mutants retain the segmental modulation of the expression of twist. Both the domain of even-skipped function and the level of twist expression are regulated by sloppy-paired. sloppy-paired thus controls segmental allocation of mesodermal cells to different fates.

Animals↗
PubMed1996

Identification of novel genes in Drosophila reveals the complex regulation of early gene activity in the mesoderm.

Two zygotic genes, twist and snail, are indispensable for the correct establishment of the mesoderm primordium in the early Drosophila embryo. They are also needed for morphogenesis and differentiation of the mesoderm. Both genes code for transcription factors with different, albeit complementary, functions. Therefore, to understand the early development of the mesoderm, it will be necessary to identify and study the genes regulated by twist and snail. We have searched for downstream genes using a subtractive cDNA library enriched in sequences expressed in the mesoderm. We have isolated sequences that correspond to 13 novel early mesoderm genes. These novel genes show a variety of expression patterns and also differ in their dependence on twist and snail functions. This indicates that the regulation of early gene activity in the mesoderm is more complex than previously thought.

Animals↗
PubMed1996

Adherens junctions in the Drosophila embryo: the role of E-cadherin in their establishment and morphogenetic function.

The integrity of epithelia depends largely on specialised adhesive structures, the adherens junctions. Several of the components required for building these structures are highly conserved between vertebrates and insects (e.g. E-cadherin and alpha- and beta-catenin), while others have so far been found only in invertebrates (e.g. crumbs). Two recent papers(1,2) show that the Drosophila E-cadherin is encoded by the gene shotgun. Phenotypic analyses of shotgun as well as armadillo (beta-catenin) and crumbs mutants provide new insights into the mechanisms by which adherens junctions are built and, further, show that the requirement for E-cadherin largely depends on the morphogenetic activity of an epithelium.

Animals↗
PubMed1996

The gelsolin-related flightless I protein is required for actin distribution during cellularisation in Drosophila.

We have analysed the developmental defects in Drosophila embryos lacking a gelsolin-related protein encoded by the gene flightless I. Such embryos have previously been reported to gastrulate abnormally. We now show that the most dramatic defects are seen earlier, in actin-dependent events during cellularisation of the syncytial blastoderm, a process with similarities to cytokinesis. The blastoderm nuclei migrate to the periphery of the egg normally but lose their precise cortical positioning during cellularisation. Cleavage membranes are initially formed, but invaginate irregularly and often fail to close at the basal end of the newly formed cells. The association of actin with the cellularisation membranes is irregular, suggesting a role for flightless I in the delivery of actin to the actin network, or in its stabilisation.

Actins↗
PubMed1995

Drosophila gastrulation: from pattern formation to morphogenesis.

The major morphogenetic movements during Drosophila gastrulation--germ band extension and the invagination of the mesoderm and endoderm--are driven by cell intercalation and cell shape changes, respectively. The regions of the early embryo in which these movements occur and which give rise to the germ layers are demarcated by a small number of zygotically expressed genes. These genes code for transcription factors that regulate cell behavior by controlling expression of target genes whose products modulate the cytoskeleton and other subcellular compartments.

Animals↗
PubMed1994

Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila, Tribolium, and Locusta.

The Brachyury (T) gene is required for notochord differentiation in vertebrates. We have identified a Drosophila gene, the T-related gene (Trg), with high similarity to T within a stretch of approximately 200 amino acids, the DNA-binding domain of T. Trg is expressed throughout embryogenesis, first at the blastoderm stage in the hindgut primordium under the control of the terminal gap genes tll and hkb, and then until the end of embryogenesis in the differentiating hindgut. Drosophila embryos deficient for Trg do not form the hindgut, a phenotype that can be rescued by a Trg transgene. Thus, a common feature of T and Trg is their requirement in specifying the development of a single embryonic structure. Homologs of Trg are also expressed in the developing hindgut of Tribolium and Locusta embryos suggesting a highly conserved function of Trg in insects. This conservation and the high similarity of T and Trg raise the question of a common evolutionary origin of the hindgut of insects and the notochord of chordates.

Amino Acid Sequence↗
PubMed1994

Identification of secreted and cytosolic gelsolin in Drosophila.

We have cloned the gene for Drosophila gelsolin. Two mRNAs are produced from this gene by differential splicing. The protein encoded by the longer mRNA has a signal peptide and its electrophoretic mobility when translated in vitro in the presence of microsomes is higher than when it is translated without microsomes. The protein translated from the shorter mRNA does not show this difference. This indicates that Drosophila like vertebrates has two forms of gelsolin, one secreted, the other cytoplasmic. The mRNA for both is present ubiquitously in the early embryo. Later, the cytoplasmic form is expressed in parts of the gut. The RNA for the secreted form is expressed in the fat body, and the secreted protein is abundant in extracellular fluid (hemolymph). The cytoplasmic form of gelsolin co-localizes with F-actin in the cortex of the cells in the embryo and in larval epithelia. However, during cellularization of the blastoderm it is reduced at the base of the cleavage furrow, a structure similar to the contractile ring in dividing cells.

Alternative Splicing↗