Morphogen concentration gradients provide positional information by activating target genes in a concentration-dependent manner. Recent reports show that the gradient of syncytial morphogen Bicoid seems to precise determine gene domains. For secreted morphogenetic ligands, precision gradients, signal transduction and reliability expression domains have not been studied. Here we investigate these issues for TGF-beta-type Dpp. We first studied theoretically how cell-to-cell variability source,...

In the Drosophila testis, germline stem cells (GSCs) and somatic cyst (CySCs) are arranged around a group of postmitotic cells, termed hub, which produce variety growth factors contributing to niche microenvironment that regulates both cell pools. Here we show CySC but not GSC maintenance requires Hedgehog (Hh) signalling in addition Jak/Stat pathway activation. clones unable transduce Hh signal lost by differentiation, whereas overactivation leads an increase proliferation. However, unlike...

The availability of the full Drosophila genomic DNA sequence prompts development a method to efficiently obtain mutations in genes interest identified by their homologies or biochemically. To date, molecularly characterized have been generated around 6000 ∼15,000 annotated fly genes, which one-third are essential for viability. and nonessential interest, we took reverse genetics approach, based on large-scale detection point Cel-I-mediated heteroduplex cleavage. A library from 2086...

During development, cells acquire positional information by reading the concentration of morphogens. In developing fly wing, a gradient transforming growth factor-beta (TGF-beta)-type morphogen decapentaplegic (Dpp) is transduced into phosphorylated form R-Smad transcription factor Mad. The endosomal protein Sara (Smad anchor for receptor activation) recruits R-Smads phosphorylation type I TGF-beta receptor. We found that Sara, Dpp, and its Thickveins were targeted to subpopulation apical...

Drosophila Cornichon (Cni) is the founding member of a conserved protein family that also includes Erv14p, an integral component COPII-coated vesicles mediate cargo export from yeast endoplasmic reticulum (ER). During oogenesis, Cni required for transport TGFα growth factor Gurken (Grk) to oocyte surface. Here, we show Cni, but not second homologue Cni-related (Cnir), binds extracellular domain Grk, and propose acts as receptor recruiting Grk into COPII vesicles. Consequently,in absence...

Adhesion between epithelial cells and extracellular substrates is normally mediated through basal adhesion complexes. However, some also possess comparable junctions on their apical surface. Here, we describe two new Drosophila proteins, Piopio Papillote, that are required for the link surface overlying matrix (aECM). The proteins share a zona pellucida (ZP) domain with mammalian aECM components, including tectorins found in vertebrate inner ear. Tagged versions of both localized to...

Many important signalling cascades operate through specialized endosomes, but a corresponding mechanism has as yet not been described for hematopoietic cytokine receptors. Based on live-cell affinity measurements, we recently proposed that ligand-induced interleukin-4 receptor (IL-4R) complex formation and thus JAK/STAT pathway activation requires local subcellular increase in density. Here, show this concentration step is provided by the internalization of IL-4R subunits constitutive,...

Abstract Background Bacterial extracellular vesicles (BEV) are increasingly recognized as a relevant mode of contactless host-microbiota communication. BEV nanoparticles pinched off from the membrane multiple bacteria and carry nucleic acid snippets functional proteins inherited their parental bacteria. While evidence suggests that act transmitters to modulate immune response, only scarce data exist whether how efficiently internalized by colonic epithelium host‘s front line in gut. This...

The development of multicellular organisms relies on an intricate choreography intercellular communication events that pattern the embryo and coordinate formation tissues organs. It is therefore not surprising developmental biology, especially using genetic model organisms, has contributed significantly to discovery functional dissection associated signal-transduction cascades. At same time, biophysical, biochemical, cell biological approaches have provided us with insights into underlying...

Transmembrane domains (TMD) connect the inner with outer world of a living cell. Single TMD containing (bitopic) receptors are particular interest, because their oligomerization seems to be common activation mechanism in cell signaling. We analyzed composition TMDs bitopic proteins within proteomes 12 model organisms. The average number strongly polar and charged residues decreases during evolution, while occurrence dimerization motif, GxxxG, remains unchanged. This may reflect avoidance...

Based on sequence divergence in the transformation-relevant region, herpesvirus saimiri strains are classified into three subgroups. Only members of subgroup C transform human T lymphocytes to continuous interleukin-2-dependent growth culture. In this study, cord blood cells were immortalized by using different (C488, C484, and C139). The resulting T-cell lines represented types clones. They either CD4+ or CD8+ expressed alphabeta gammadelta type receptors. If transformed same virus strain,...

Whereas stem and progenitor cells proliferate to maintain tissue homeostasis, fully differentiated exit the cell cycle. How identity cell-cycle state are coordinated during differentiation is still poorly understood. The Drosophila testis niche supports germline somatic cyst (CySCs). CySCs give rise post-mitotic cells, providing a tractable model study links between proliferation. We show that, while progression required for CySC self-renewal, E2f1/Dp transcription factor dispensable...

ABSTRACT Niches have traditionally been characterised as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes the various niche signals are integrated towards a binary fate decision between stemness and differentiation. However, observations in multiple systems demonstrated cell properties, such proliferation self-renewal, can be uncoupled at level of input, which is incompatible with this simplified view. We studied role...

The Hedgehog (Hh) signalling cascade is highly conserved and involved in development disease throughout evolution. Nevertheless, comparison with other pathways our mechanistic understanding of Hh signal transduction remarkably incomplete. In the absence ligand, receptor Patched (Ptc) represses key transducer Smoothened (Smo) through an unknown mechanism. binding to Ptc alleviates this repression, causing Smo redistribution plasma membrane, phosphorylation opening cytoplasmic tail,...

Abstract In the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for surrounding germline and somatic stem cells. Stem both populations compete physical retention in niche, cell clones unable to transduce any one signal are rapidly eliminated by differentiation. We have recently mapped transcriptomes isolated cyst differentiated cells, found that but not their progeny activate an immune response involving NF-κB transcription factor Relish (Rel). Here we...

The Hedgehog (Hh) signalling cascade plays an important role in development and disease. In the absence of Hh ligand, activity key signal transducer Smoothened (Smo) is downregulated by receptor Patched (Ptc). However, mechanisms underlying this inhibition, especially its release upon ligand stimulation, are still poorly understood, part because tools for following Smo activation at subcellular level were long lacking. To address deficit we have developed a high throughput cell culture assay...

In the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for surrounding germline and somatic stem cells. Stem both populations compete physical retention in niche, clones unable to transduce any one signal are rapidly eliminated from cell pool by differentiation. We have mapped transcriptomes isolated cyst differentiated cells, found that but not their progeny exhibit signature an innate immune response including NF-κB transcription factor Relish (Rel)....

Abstract Niches have traditionally been characterized as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes the various niche signals are integrated towards a binary fate decision between stemness and differentiation. However, observations in multiple systems demonstrated cell properties such proliferation self renewal can be uncoupled at level of input, which is incompatible with this simplified view. We studied role transcriptional...