Proximal to distal cell communication in the Drosophila leg provides a basis for an intercalary mechanism of limb patterning

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3407-3413 ◽  
Author(s):  
S. Goto ◽  
S. Hayashi

Proximodistal patterning in the Drosophila leg is elaborated from the circular arrangement of the proximal domain expressing escargot and homothorax, and the distal domain expressing Distal-less that are allocated during embryogenesis. The distal domain differentiates multiply segmented distal appendages by activating additional genes such as dachshund. Secreted signaling molecules Wingless and Decapentaplegic, expressed along the anterior-posterior compartment boundary, are required for activation of Distal-less and dachshund and repression of homothorax in the distal domain. However, whether Wingless and Decapentaplegic are sufficient for the circular pattern of gene expression is not known. Here we show that a proximal gene escargot and its activator homothorax regulate proximodistal patterning in the distal domain. Clones of cells expressing escargot or homothorax placed in the distal domain induce intercalary expression of dachshund in surrounding cells and reorient planar cell polarity of those cells. Escargot and homothorax-expressing cells also sort out from other cells in the distal domain. We suggest that inductive cell communication between the proximodistal domains, which is maintained in part by a cell-sorting mechanism, is the cellular basis for an intercalary mechanism of the proximodistal axis patterning of the limb.


Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1427-1438 ◽  
Author(s):  
Mátyás Végh ◽  
Konrad Basler

Abstract The development of multicellular organisms requires the establishment of cell populations with different adhesion properties. In Drosophila, a cell-segregation mechanism underlies the maintenance of the anterior (A) and posterior (P) compartments of the wing imaginal disc. Although engrailed (en) activity contributes to the specification of the differential cell affinity between A and P cells, recent evidence suggests that cell sorting depends largely on the transduction of the Hh signal in A cells. The activator form of Cubitus interruptus (Ci), a transcription factor mediating Hh signaling, defines anterior specificity, indicating that Hh-dependent cell sorting requires Hh target gene expression. However, the identity of the gene(s) contributing to distinct A and P cell affinities is unknown. Here, we report a genetic screen based on the FRT/FLP system to search for genes involved in the correct establishment of the anteroposterior compartment boundary. By using double FRT chromosomes in combination with a wing-specific FLP source we screened 250,000 mutagenized chromosomes. Several complementation groups affecting wing patterning have been isolated, including new alleles of most known Hh-signaling components. Among these, we identified a class of patched (ptc) alleles exhibiting a novel phenotype. These results demonstrate the value of our setup in the identification of genes involved in distinct wing-patterning processes.





2014 ◽  
Vol 369 (1652) ◽  
pp. 20130502 ◽  
Author(s):  
Mu Li ◽  
Emily Zeringer ◽  
Timothy Barta ◽  
Jeoffrey Schageman ◽  
Angie Cheng ◽  
...  

Exosomes are tiny vesicles (30–150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer.



2021 ◽  
Vol 49 (4) ◽  
pp. 1779-1790 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Chiara Giacomelli ◽  
Laura Marchetti ◽  
Claudia Martini

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.



Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4053-4063 ◽  
Author(s):  
S.S. Blair ◽  
A. Ralston

It is thought that the posterior expression of the ‘selector’ genes engrailed and invected control the subdivision of the growing wing imaginal disc of Drosophila into anterior and posterior lineage compartments. At present, the cellular mechanisms by which separate lineage compartments are maintained are not known. Most models have assumed that the presence or absence of selector gene expression autonomously drives the expression of compartment-specific adhesion or recognition molecules that inhibit intermixing between compartments. However, our present understanding of Hedgehog signalling from posterior to anterior cells raises some interesting alternative models based on a cell's response to signalling. We show here that anterior cells that lack smoothened, and thus the ability to receive the Hedgehog signal, no longer obey a lineage restriction in the normal position of the anterior-posterior boundary. Rather these clones extend into anatomically posterior territory, without any changes in engrailed/invected gene expression. We have also examined clones lacking both en and inv; these too show complex behaviors near the normal site of the compartment boundary, and do not always cross entirely into anatomically anterior territory. Our results suggest that compartmentalization is a complex process involving intercompartmental signalling; models based on changes in affinity or growth will be discussed.



2018 ◽  
Vol 19 (12) ◽  
pp. 4124 ◽  
Author(s):  
Antonella Raffo-Romero ◽  
Tanina Arab ◽  
Issa Al-Amri ◽  
Francoise Le Marrec-Croq ◽  
Christelle Van Camp ◽  
...  

In healthy or pathological brains, the neuroinflammatory state is supported by a strong communication involving microglia and neurons. Recent studies indicate that extracellular vesicles (EVs), including exosomes and microvesicles, play a key role in the physiological interactions between cells allowing central nervous system (CNS) development and/or integrity. The present report used medicinal leech CNS to investigate microglia/neuron crosstalk from ex vivo approaches as well as primary cultures. The results demonstrated a large production of exosomes from microglia. Their incubation to primary neuronal cultures showed a strong interaction with neurites. In addition, neurite outgrowth assays demonstrated microglia exosomes to exhibit significant neurotrophic activities using at least a Transforming Growth Factor beta (TGF-β) family member, called nGDF (nervous Growth/Differentiation Factor). Of interest, the results also showed an EV-mediated dialog between leech microglia and rat cells highlighting this communication to be more a matter of molecules than of species. Taken together, the present report brings a new insight into the microglia/neuron crosstalk in CNS and would help deciphering the molecular evolution of such a cell communication in brain.



2020 ◽  
Author(s):  
O. Cochet-Escartin ◽  
M. Demircigil ◽  
S. Hirose ◽  
B. Allais ◽  
P. Gonzalo ◽  
...  

AbstractIt is well known that eukaryotic cells can sense oxygen (O2) and adapt their metabolism accordingly. It is less known that they can also move towards regions of higher oxygen level (aerotaxis). Using a self-generated hypoxic assay, we show that the social amoeba Dictyostelium discoideum displays a spectacular aerotactic behavior. When a cell colony is covered by a coverglass, cells quickly consume the available O2 and the ones close to the periphery move directionally outward forming a dense ring keeping a constant speed and density. To confirm that O2 is the main molecular player in this seemingly collective process, we combined two technological developments, porphyrin based O2 sensing films and microfluidic O2 gradient generators. We showed that Dictyostelium cells exhibit aerotactic and aerokinetic (increased speed at low O2) response in an extremely low range of O2 concentration (0-1.5%) indicative of a very efficient detection mechanism. The various cell behaviors under self-generated or imposed O2 gradients were modeled with a very satisfactory quantitative agreement using an in silico cellular Potts model built on experimental observations. This computational model was complemented with a parsimonious ‘Go or Grow’ partial differential equation (PDE) model. In both models, we found that the collective migration of a dense ring can be explained by the interplay between cell division and the modulation of aerotaxis, without the need for cell-cell communication.



Life ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 38 ◽  
Author(s):  
Masayuki Hayakawa ◽  
Satoshi Umeyama ◽  
Ken Nagai ◽  
Hiroaki Onoe ◽  
Masahiro Takinoue

Recently, the construction of models for multicellular systems such as tissues has been attracting great interest. These model systems are expected to reproduce a cell communication network and provide insight into complicated functions in living systems./Such network structures have mainly been modelled using a droplet and a vesicle. However, in the droplet and vesicle network, there are difficulties attributed to structural instabilities due to external stimuli and perturbations. Thus, the fabrication of a network composed of a stable component such as hydrogel is desired. In this article, the construction of a stable network composed of honeycomb-shaped microhydrogels is described. We produced the microhydrogel network using a centrifugal microfluidic technique and a photosensitive polymer. In the network, densely packed honeycomb-shaped microhydrogels were observed. Additionally, we successfully controlled the degree of packing of microhydrogels in the network by changing the centrifugal force. We believe that our stable network will contribute to the study of cell communication in multicellular systems.



Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 589-599 ◽  
Author(s):  
M. Ng ◽  
F.J. Diaz-Benjumea ◽  
S.M. Cohen

The nubbin gene is required for normal growth and patterning of the wing in Drosophila. We report here that nubbin encodes a member of the POU family of transcription factors. Regulatory mutants which selectively remove nubbin expression from wing imaginal discs lead to loss of wing structures. Although nubbin is expressed throughout the wing primordium, analysis of genetic mosaics suggests a localized requirement for nubbin activity in the wing hinge. These observations suggest the existence of a novel proximal-distal growth control center in the wing hinge, which is required in addition to the well characterized anterior-posterior and dorsal-ventral compartment boundary organizing centers.



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