scholarly journals Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3105-3117 ◽  
Author(s):  
M. Affolter ◽  
D. Nellen ◽  
U. Nussbaumer ◽  
K. Basler
Keyword(s):  
Cell Communication ◽  
Cell Types ◽  
Dorsal Closure ◽  
Homeotic Genes ◽  
Embryonic Cells ◽  
Tgf Beta ◽  
Loss Of Function ◽  
Surface Receptors ◽  
Visceral Mesoderm ◽  
Distinct Cell

Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

scholarly journals Misregulation of SDF1-CXCR4 Signaling Impairs Early Cardiac Neural Crest Cell Migration Leading to Conotruncal Defects

2013 ◽  
Vol 113 (5) ◽  
pp. 505-516 ◽  
Author(s):  
Sophie Escot ◽  
Cédrine Blavet ◽  
Sonja Härtle ◽  
Jean-Loup Duband ◽  
Claire Fournier-Thibault
Keyword(s):  
Neural Crest ◽  
Molecular Mechanisms ◽  
Heart Diseases ◽  
Smooth Muscles ◽  
Neural Crest Cell ◽  
Cell Types ◽  
Ventricular Septum ◽  
Embryonic Cells ◽  
Loss Of Function ◽  
Cardiac Neural Crest

Rationale: Cardiac neural crest cells (NCs) contribute to heart morphogenesis by giving rise to a variety of cell types from mesenchyme of the outflow tract, ventricular septum, and semilunar valves to neurons of the cardiac ganglia and smooth muscles of the great arteries. Failure in cardiac NC development results in outflow and ventricular septation defects commonly observed in congenital heart diseases. Cardiac NCs derive from the vagal neural tube, which also gives rise to enteric NCs that colonize the gut; however, so far, molecular mechanisms segregating these 2 populations and driving cardiac NC migration toward the heart have remained elusive. Objective: Stromal-derived factor-1 (SDF1) is a chemokine that mediates oriented migration of multiple embryonic cells and mice deficient for Sdf1 or its receptors, Cxcr4 and Cxcr7 , exhibit ventricular septum defects, raising the possibility that SDF1 might selectively drive cardiac NC migration toward the heart via a chemotactic mechanism. Methods and Results : We show in the chick embryo that Sdf1 expression is tightly coordinated with the progression of cardiac NCs expressing Cxcr4 . Cxcr4 loss-of-function causes delayed migration and enhanced death of cardiac NCs, whereas Sdf1 misexpression results in their diversion from their normal pathway, indicating that SDF1 acts as a chemoattractant for cardiac NCs. These alterations of SDF1 signaling result in severe cardiovascular defects. Conclusions: These data identify Sdf1 and its receptor Cxcr4 as candidate genes responsible for cardiac congenital pathologies in human.

scholarly journals Epidermal control of floral organ identity by class B homeotic genes in Antirrhinum and Arabidopsis

Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2661-2671
Author(s):  
Nadia Efremova ◽  
Marie-Christine Perbal ◽  
Alexander Yephremov ◽  
Winfried A. Hofmann ◽  
Heinz Saedler ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Transgenic Arabidopsis ◽  
Cell Communication ◽  
Cell Types ◽  
Floral Organ ◽  
Epidermal Differentiation ◽  
Homeotic Genes ◽  
Organ Identity ◽  
Class B ◽  
Functional Homologues

To assess the contribution of the epidermis to the control of petal and stamen organ identity, we have used transgenic Antirrhinum and Arabidopsis plants that expressed the Antirrhinum class B homeotic transcription factors DEFICIENS (DEF) and GLOBOSA (GLO) in the epidermis. Transgene expression was controlled by the ANTIRRHINUM FIDDLEHEAD (AFI) promoter, which directs gene expression to the L1 meristematic layer and, later, to the epidermis of differentiating organs. Transgenic epidermal DEF and GLO chimeras display similar phenotypes, suggesting similar epidermal contributions by the two class B genes in Antirrhinum. Epidermal B function autonomously controls the differentiation of Antirrhinum petal epidermal cell types, but cannot fully control the pattern of cell divisions and the specification of sub-epidermal petal cell-identity by epidermal signalling. This non-autonomous control is enhanced if the endogenous class B genes can be activated from the epidermis. The developmental influence of epidermal B function in Antirrhinum stamen development is very limited. In contrast, epidermal B function in Arabidopsis can control most if not all epidermal and sub-epidermal differentiation events in petals and stamens, without any contribution from the endogenous class B genes. Possible reasons for differences in the efficacy of B-function-mediated cell communication between the two species are discussed. Interestingly, our experiments uncovered partial incompatibility between class B functional homologues. Although the DEFICIENS/PISTILLATA heterodimer is functional in transgenic Arabidopsis plants, the APETALA3/GLOBOSA heterodimer is not.

scholarly journals A draft network of ligand–receptor-mediated multicellular signalling in human

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Jordan A. Ramilowski ◽  
Tatyana Goldberg ◽  
Jayson Harshbarger ◽  
Edda Kloppmann ◽  
Marina Lizio ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Surface Receptors ◽  
Signalling Network ◽  
Multiple Cell ◽  
Autocrine Signalling ◽  
Multiple Ligand

Abstract Cell-to-cell communication across multiple cell types and tissues strictly governs proper functioning of metazoans and extensively relies on interactions between secreted ligands and cell-surface receptors. Herein, we present the first large-scale map of cell-to-cell communication between 144 human primary cell types. We reveal that most cells express tens to hundreds of ligands and receptors to create a highly connected signalling network through multiple ligand–receptor paths. We also observe extensive autocrine signalling with approximately two-thirds of partners possibly interacting on the same cell type. We find that plasma membrane and secreted proteins have the highest cell-type specificity, they are evolutionarily younger than intracellular proteins, and that most receptors had evolved before their ligands. We provide an online tool to interactively query and visualize our networks and demonstrate how this tool can reveal novel cell-to-cell interactions with the prediction that mast cells signal to monoblastic lineages via the CSF1–CSF1R interacting pair.

scholarly journals Genomic regions required for morphogenesis of the Drosophila embryonic midgut.

Genetics ◽  
1995 ◽  
Vol 141 (3) ◽  
pp. 1087-1100 ◽  
Author(s):  
D Bilder ◽  
M P Scott
Keyword(s):  
Regulatory Gene ◽  
Cell Communication ◽  
Gene Families ◽  
Genomic Region ◽  
Hormonal Control ◽  
Homeotic Genes ◽  
Spatial Regulation ◽  
Visceral Mesoderm ◽  
Genomic Regions ◽  
Midgut Development

Abstract The Drosophila midgut is an excellent system for studying the cell migration, cell-cell communication, and morphogenetic events that occur in organ formation. Genes representative of regulatory gene families common to all animals, including homeotic, TGF beta, and Wnt genes, play roles in midgut development. To find additional regulators of midgut morphogenesis, we screened a set of genomic deficiencies for midgut phenotypes. Fifteen genomic intervals necessary for proper midgut morphogenesis were identified, three contain genes already known to act in the midgut. Three other genomic regions are required for formation of the endoderm or visceral mesoderm components of the midgut. Nine regions are required for proper formation of the midgut constrictions. The E75 ecdysone-induced gene, which encodes a nuclear receptor superfamily member, is the relevant gene in one region and is essential for proper formation of midgut constrictions. E75 acts downstream of the previously known constriction regulators or in parallel. Temporal hormonal control may therefore work in conjunction with spatial regulation by the homeotic genes in midgut development. Another genomic region is required to activate transcription of the homeotic genes Antp and Scr specifically in visceral mesoderm. The genomic regions identified by this screen provide a map to novel midgut development regulators.

scholarly journals NvPOU4/Brain3 functions as a terminal selector gene in the nervous system of the cnidarian Nematostella vectensis

2020 ◽  
Author(s):  
Océane Tournière ◽  
David Dolan ◽  
Gemma Sian Richards ◽  
Kartik Sunagar ◽  
Yaara Y Columbus-Shenkar ◽  
...  
Keyword(s):  
Terminal Differentiation ◽  
Cell Types ◽  
Neural Cell ◽  
Nematostella Vectensis ◽  
Cell Populations ◽  
Neural Cells ◽  
Loss Of Function ◽  
Molecular Features ◽  
Cnidarian Nematostella Vectensis ◽  
Distinct Cell

SUMMARYTerminal selectors are transcription factors that control the morphological, physiological and molecular features that characterize distinct cell types. Here we use expression analyses and a transgenic reporter line to show that NvPOU4 is expressed in post-mitotic cells that give rise to a diverse set of neural cell types in the sea anemone Nematostella vectensis. We generated a loss-of-function allele by CRISPR/Cas9 and used additional transgenic reporter lines to show that the initial specification of neural cells is not affected in the NvPOU4 mutants. Analyses of transcriptomes derived from the mutants and from different neural cell populations revealed that NvPOU4 is required for the execution of the terminal differentiation program of these neural cells. These findings suggest that POU4 genes have ancient functions as terminal selectors for morphologically and functionally highly disparate types of neurons and they provide experimental support for the relevance of terminal selectors for understanding the evolution of cell types.

scholarly journals Syntenin mediates SRC function in exosomal cell-to-cell communication

2017 ◽  
Vol 114 (47) ◽  
pp. 12495-12500 ◽  
Author(s):  
Naga Sailaja Imjeti ◽  
Kerstin Menck ◽  
Antonio Luis Egea-Jimenez ◽  
Celine Lecointre ◽  
Frederique Lembo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Intracellular Signaling ◽  
Cell Communication ◽  
Small Gtpase ◽  
Signaling Cascades ◽  
Current View ◽  
Loss Of Function ◽  
Surface Receptors ◽  
Host Interactions ◽  
Phospholipase D2

The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes. Exosomes are viral-like particles from endosomal origin that can reprogram recipient cells. By gain- and loss-of-function studies, we establish that SRC stimulates the secretion of exosomes having promigratory activity on endothelial cells and that syntenin is mandatory for SRC exosomal function. Mechanistically, SRC impacts on syndecan endocytosis and on syntenin–syndecan endosomal budding, upstream of ARF6 small GTPase and its effector phospholipase D2, directly phosphorylating the conserved juxtamembrane DEGSY motif of the syndecan cytosolic domain and syntenin tyrosine 46. Our study uncovers a function of SRC in cell–cell communication, supported by syntenin exosomes, which is likely to contribute to tumor–host interactions.

scholarly journals Extracellular vesicles: mediators of intercellular communication in tissue injury and disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Greg Berumen Sánchez ◽  
Kaitlyn E. Bunn ◽  
Heather H. Pua ◽  
Marjan Rafat
Keyword(s):  
Intercellular Communication ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Of Origin ◽  
Cytokines And Chemokines ◽  
Cellular Debris ◽  
Distinct Cell ◽  
High Prevalence

AbstractIntercellular communication is a critical process that ensures cooperation between distinct cell types and maintains homeostasis. EVs, which were initially described as cellular debris and devoid of biological function, are now recognized as key components in cell–cell communication. EVs are known to carry multiple factors derived from their cell of origin, including cytokines and chemokines, active enzymes, metabolites, nucleic acids, and surface molecules, that can alter the behavior of recipient cells. Since the cargo of EVs reflects their parental cells, EVs from damaged and dysfunctional tissue environments offer an abundance of information toward elucidating the molecular mechanisms of various diseases and pathological conditions. In this review, we discuss the most recent findings regarding the role of EVs in the progression of cancer, metabolic disorders, and inflammatory lung diseases given the high prevalence of these conditions worldwide and the important role that intercellular communication between immune, parenchymal, and stromal cells plays in the development of these pathological states. We also consider the clinical applications of EVs, including the possibilities for their use as novel therapeutics.

Fine Structure of the Malpighian Tubules of the Mosquito, Culex pipiens

1971 ◽  
Vol 29 ◽  
pp. 402-403
Author(s):  
Brendan Clifford
Keyword(s):  
Fine Structure ◽  
Culex Pipiens ◽  
Stellate Cell ◽  
Malpighian Tubule ◽  
Cell Types ◽  
Instar Larva ◽  
Malpighian Tubules ◽  
Calliphora Erythrocephala ◽  
Distinct Cell ◽  
Basal Plasma

An ultrastructural investigation of the Malpighian tubules of the fourth instar larva of Culex pipiens was undertaken as part of a continuing study of the fine structure of transport epithelia.Each of the five Malpighian tubules was found to be morphologically identical and regionally undifferentiated. Two distinct cell types, the primary and stellate, were found intermingled along the length of each tubule. The ultrastructure of the stellate cell was previously described in the Malpighian tubule of the blowfly, Calliphora erythrocephala by Berridge and Oschman.The basal plasma membrane of the primary cell is extremely irregular, giving rise to a complex interconnecting network of basal channels. The compartments of cytoplasm entrapped within this system of basal infoldings contain mitochondria, free ribosomes, and small amounts of rough endoplasmic reticulum. The mitochondria are distinctive in that the cristae run parallel to the long axis of the organelle.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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