The helix-loop-helix extramacrochaetae protein is required for proper specification of many cell types in the Drosophila embryo

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2555-2566 ◽  
Author(s):  
P. Cubas ◽  
J. Modolell ◽  
M. Ruiz-Gomez
Keyword(s):  
Cell Types ◽  
Drosophila Embryo ◽  
Cell Contact ◽  
Cell Recognition ◽  
Cell Specification ◽  
Helix Loop Helix ◽  
Attachment Sites ◽  
Different Cell Types ◽  
Derivatives Of ◽  
Basic Region

The Drosophila Extramacrochaetae protein antagonizes the proneural function of the Achaete and Scute proteins in the generation of the adult fly sensory organs. Extra-macrochaetae sequesters these basic-region-helix-loop-helix transcription factors as heterodimers inefficient for binding to DNA. We show that, during embryonic development, the extramacrochaetae gene is expressed in complex patterns that comprise derivatives of the three embryonic layers. Expression of extramacrochaetae often precedes and accompanies morphogenetic movements. It also occurs at regions of specialized cell-cell contact and/or cell recognition, like the epidermal part of the muscle attachment sites and the differentiating CNS. The insufficiency of extramacrochaetae affects most tissues where it is expressed. The defects suggest faulty specification of different cell types and result in impairment of processes as diverse as cell proliferation and commitment, cell adhesion and cell recognition. If Extramacrochaetae participates in cell specification by dimerizing with basic-region-helix-loop-helix proteins, the variety of defects and tissues affected by the insufficiency of extramacrochaetae suggests that helix-loop-helix proteins are involved in many embryonic developmental processes.

Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3305-3312 ◽  
Author(s):  
H.L. Ashe ◽  
M. Mannervik ◽  
M. Levine
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Histone Acetyltransferase ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Present Evidence ◽  
Drosophila Homolog ◽  
Dorsal Ectoderm ◽  
Transgenic Embryos ◽  
Different Cell Types

The dorsal ectoderm of the Drosophila embryo is subdivided into different cell types by an activity gradient of two TGF(β) signaling molecules, Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this gradient depend on a secreted inhibitor, Short gastrulation (Sog) and a newly identified transcriptional repressor, Brinker (Brk), which are expressed in neurogenic regions that abut the dorsal ectoderm. Here we examine the expression of a number of Dpp target genes in transgenic embryos that contain ectopic stripes of Dpp, Sog and Brk expression. These studies suggest that the Dpp/Scw activity gradient directly specifies at least three distinct thresholds of gene expression in the dorsal ectoderm of gastrulating embryos. Brk was found to repress two target genes, tailup and pannier, that exhibit different limits of expression within the dorsal ectoderm. These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression. We also present evidence that the activation of Dpp/Scw target genes depends on the Drosophila homolog of the CBP histone acetyltransferase.

The localized assembly of extracellular matrix integrin ligands requires cell-cell contact

2000 ◽  
Vol 113 (21) ◽  
pp. 3715-3723 ◽  
Author(s):  
M.D. Martin-Bermudo ◽  
N.H. Brown
Keyword(s):  
Extracellular Matrix ◽  
Drosophila Embryo ◽  
Cell Contact ◽  
Primary Role ◽  
Dependent Manner ◽  
Muscle Attachment ◽  
Matrix Assembly ◽  
Attachment Sites ◽  
Genetically Manipulated ◽  
Cell Cell

The assembly of an organism requires the interaction between different layers of cells, in many cases via an extracellular matrix. In the developing Drosophila larva, muscles attach in an integrin-dependent manner to the epidermis, via a specialized extracellular matrix called tendon matrix. Tiggrin, a tendon matrix integrin ligand, is primarily synthesized by cells distant to the muscle attachment sites, yet it accumulates specifically at these sites. Previous work has shown that the PS integrins are not required for tiggrin localization, suggesting that there is redundancy among tiggrin receptors. We have examined this by testing whether the PS2 integrin can recruit tiggrin to ectopic locations within the Drosophila embryo. We found that neither the wild type nor modified forms of the PS2 integrin, which have higher affinity for tiggrin, can recruit tiggrin to new cellular contexts. Next, we genetically manipulated the fate of the muscles and the epidermal muscle attachment cells, which demonstrated that muscles have the primary role in recruiting tiggrin to the tendon matrix and that cell-cell contact is necessary for this recruitment. Thus we propose that the inherent polarity of the muscle cells leads to a molecular specialization of their ends, and interactions between the ends produces an integrin-independent tiggrin receptor. Thus, interaction between cells generates an extracellular environment capable of nucleating extracellular matrix assembly.

Gonadal mesoderm and fat body initially follow a common developmental path in Drosophila

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 837-844 ◽  
Author(s):  
L.A. Moore ◽  
H.T. Broihier ◽  
M. Van Doren ◽  
R. Lehmann
Keyword(s):  
Cell Fate ◽  
Fat Body ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Body Development ◽  
Developmental Relationship ◽  
Close Juxtaposition ◽  
Fate Decision ◽  
Different Cell Types ◽  
Lateral Mesoderm

During gastrulation, the Drosophila mesoderm invaginates and forms a single cell layer in close juxtaposition to the overlying ectoderm. Subsequently, particular cell types within the mesoderm are specified along the anteroposterior and dorsoventral axes. The exact developmental pathways that guide the specification of different cell types within the mesoderm are not well understood. We have analyzed the developmental relationship between two mesodermal tissues in the Drosophila embryo, the gonadal mesoderm and the fat body. Both tissues arise from lateral mesoderm within the eve domain. Whereas in the eve domain of parasegments 10–12 gonadal mesoderm develops from dorsolateral mesoderm and fat body from ventrolateral mesoderm, in parasegments 4–9 only fat body is specified. Our results demonstrate that the cell fate decision between gonadal mesoderm and fat body identity within dorsolateral mesoderm along the anteroposterior axis is determined by the combined actions of genes including abdA, AbdB and srp; while srp promotes fat body development, abdA allows gonadal mesoderm to develop by repressing srp function. Furthermore, we present evidence from genetic analysis suggesting that, before stage 10 of embryogenesis, gonadal mesoderm and the fat body have not yet been specified as different cell types, but exist as a common pool of precursor cells requiring the functions of the tin, zfh-1 and cli genes for their development.

Integrins modulate the Egfr signaling pathway to regulate tendon cell differentiation in the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2607-2615 ◽  
Author(s):  
M.D. Martin-Bermudo
Keyword(s):  
Cell Differentiation ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Muscle Attachment ◽  
Tendon Cell ◽  
Egfr Signaling Pathway ◽  
Attachment Sites ◽  
The Individual ◽  
Muscle Attachment Sites

Changes in the extracellular matrix (ECM) govern the differentiation of many cell types during embryogenesis. Integrins are cell matrix receptors that play a major role in cell-ECM adhesion and in transmitting signals from the ECM inside the cell to regulate gene expression. In this paper, it is shown that the PS integrins are required at the muscle attachment sites of the Drosophila embryo to regulate tendon cell differentiation. The analysis of the requirements of the individual alpha subunits, alphaPS1 and alphaPS2, demonstrates that both PS1 and PS2 integrins are involved in this process. In the absence of PS integrin function, the expression of tendon cell-specific genes such as stripe and beta1 tubulin is not maintained. In addition, embryos lacking the PS integrins also exhibit reduced levels of activated MAPK. This reduction is probably due to a downregulation of the Epidermal Growth Factor receptor (Egfr) pathway, since an activated form of the Egfr can rescue the phenotype of embryos mutant for the PS integrins. Furthermore, the levels of the Egfr ligand Vein at the muscle attachment sites are reduced in PS mutant embryos. Altogether, these results lead to a model in which integrin-mediated adhesion plays a role in regulating tendon cell differentiation by modulating the activity of the Egfr pathway at the level of its ligand Vein.

scholarly journals Using stem cells to study and possibly treat type 1 diabetes

2011 ◽  
Vol 366 (1575) ◽  
pp. 2307-2311 ◽  
Author(s):  
D. A. Melton
Keyword(s):  
Stem Cells ◽  
Cell Types ◽  
Juvenile Diabetes ◽  
Degenerative Diseases ◽  
Cell Replacement ◽  
Disease Phenotypes ◽  
New Treatments ◽  
Different Cell Types ◽  
Derivatives Of

Stem cells with the potential to form many different cell types are actively studied for their possible use in cell replacement therapies for several diseases. In addition, the differentiated derivatives of stem cells are being used as reagents to test for drugs that slow or correct disease phenotypes found in several degenerative diseases. This paper explores these approaches in the context of type 1 or juvenile diabetes, pointing to recent successes as well as the technical and theoretical challenges that lie ahead in the path to new treatments and cures.

scholarly journals A minibead method for detection of membrane lectins.

1989 ◽  
Vol 37 (1) ◽  
pp. 91-96 ◽  
Author(s):  
T Matsuoka ◽  
M Tavassoli
Keyword(s):  
Soluble Sugar ◽  
Cell Types ◽  
Cell Populations ◽  
Morphological Identification ◽  
Cell Systems ◽  
Biological Phenomena ◽  
Homogeneous Cell ◽  
Different Cell Types ◽  
Derivatives Of ◽  
Scanning Electron

Membrane lectins are being increasingly implicated in many biological phenomena. Previous methods for detection of these substances are applicable only to homogeneous cell populations. We have now developed a method that permits morphological identification of lectin-bearing cells in heterogeneous cell populations. Amide-modified latex minibeads (0.345 or 0.532 micron) were activated with glutaraldehyde and then covalently bound to p-aminophenyl derivatives of various sugars. When the probe thus constructed was incubated with cell systems known to bear well-defined membrane lectins (galactosyl receptors in hepatocytes, mannosyl receptors in macrophages), binding occurred and could be visualized by scanning electron microscopy. Binding was inhibited in the presence of excess soluble sugar, indicating the specificity of reaction. Incubation of a mixture of two different-sized probes with two different cell types led to segregation of the probes. This method also permits semiquantification of binding.

scholarly journals Functional Replacement of the Mouse E2A Gene with a Human HEB cDNA

1998 ◽  
Vol 18 (6) ◽  
pp. 3340-3349 ◽  
Author(s):  
Yuan Zhuang ◽  
Robert J. Barndt ◽  
Lihua Pan ◽  
Robert Kelley ◽  
Meifang Dai
Keyword(s):  
B Lymphocyte ◽  
Functional Divergence ◽  
Cell Types ◽  
Mammalian Development ◽  
Helix Loop Helix ◽  
Alternatively Spliced ◽  
Cell Commitment ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins ◽  
Different Cell Types

ABSTRACT The mammalian E2A, HEB, and E2-2 genes encode a unique class of basic helix-loop-helix (bHLH) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development. While the structural and functional similarities among the gene products are well demonstrated, it is not clear why deletion of E2A, but not HEB or E2-2, leads to a complete arrest in B-lymphocyte development. To understand the molecular basis of the functional specificity between E2A and HEB/E2-2 in mammalian development, we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA. We find that the alternatively spliced E12 and E47 bHLH proteins of the E2A gene play similar and additive roles in supporting B lymphopoiesis. Further, we find that HEB driven by the endogenous E2A promoter can functionally replace E2A in supporting B-cell commitment and differentiation toward completion. Finally, the postnatal lethality associated with E2A disruption is fully rescued by the addition of HEB. This study suggests that the functional divergence among E12, E47, and HEB in different cell types is partially defined by the context of gene expression.

scholarly journals GLI ESOSOMI NELLA COMUNICAZIONE CELLULA-CELLULA

2020 ◽  
Author(s):  
Stefania Raimondo
Keyword(s):  
Small Molecules ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Contact ◽  
Bioactive Lipids ◽  
Pathological Conditions ◽  
Extracellular Matrix Components ◽  
Different Cell Types ◽  
Cell Cell

Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years a new and sophisticated mechanism of cell-cell communication based on extracellular vesicles has been described. Extracellular vesicles are specialized vesicles released in the extracellular space by most of cell types, under physiological and pathological conditions. Among different extracellular vesicles subtypes, exosomes (30-100 nm) have recently received most of the attention do to their ability to be messenger in intercellular communication.

Chemical Synthesis, Mechanism of Action and Anticancer Potential of Medicinally Important Thiazolidin-2,4-dione Derivatives: A Review

2019 ◽  
Vol 19 (18) ◽  
pp. 1474-1516 ◽  
Author(s):  
Harsh Kumar ◽  
Aakash Deep ◽  
Rakesh Kumar Marwaha
Keyword(s):  
Anticancer Activity ◽  
Mechanism Of Action ◽  
Cell Types ◽  
New Drugs ◽  
Synthesis Mechanism ◽  
Biological Potential ◽  
Proliferation And Apoptosis ◽  
Target Molecules ◽  
Different Cell Types ◽  
Derivatives Of

Thiazolidin-2,4-dione (TZD) possessing an active methylene constitute an important chemical class of compounds for the development of new drugs. So, many scholars have synthesized these derivatives as target molecules and evaluated their biological potential. Currently, some of the TZDs are synthesized to treat human cancers stating high levels of PPARγ because it is expected that activation of PPARγ arbitrates their anticancer activity because PPARγ ligands have recently been established to affect differentiation, cell proliferation and apoptosis of different cell types. In the present review, the synthesis of various derivatives of thiazolidine-2,4-diones, their mechanism of action and anticancer activity have been highlighted.

scholarly journals Induction of Endothelial PAS Domain Protein-1 by Hypoxia: Characterization and Comparison With Hypoxia-Inducible Factor-1α

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2260-2268 ◽  
Author(s):  
M.S. Wiesener ◽  
H. Turley ◽  
W.E. Allen ◽  
C. Willam ◽  
K.-U. Eckardt ◽  
...  
Keyword(s):  
Mutant Cell ◽  
Hypoxia Inducible Factor ◽  
Cell Types ◽  
Pas Domain ◽  
Functional Studies ◽  
Hypoxia Inducible Factor 1 ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Domain Protein ◽  
Different Cell Types

Abstract Hypoxia results in adaptive changes in the transcription of a range of genes including erythropoietin. An important mediator is hypoxia-inducible factor-1 (HIF-1), a DNA binding complex shown to contain at least two basic helix-loop-helix PAS-domain (bHLH-PAS) proteins, HIF-1α and aryl hydrocarbon nuclear receptor translocator (ARNT). In response to hypoxia, HIF-1α is activated and accumulates rapidly in the cell. Endothelial PAS domain protein 1 (EPAS-1) is a recently identified bHLH-PAS protein with 48% identity to HIF-1α, raising the question of its role in responses to hypoxia. We developed specific antibodies and studied expression and regulation of EPAS-1 mRNA and protein across a range of human cell lines. EPAS-1 was widely expressed, and strongly induced by hypoxia at the level of protein but not mRNA. Comparison of the effect of a range of activating and inhibitory stimuli showed striking similarities in the EPAS-1 and HIF-1α responses. Although major differences were observed in the abundance of EPAS-1 and HIF-1α in different cell types, differences in the inducible response were subtle with EPAS-1 protein being slightly more evident in normoxic and mildly hypoxic cells. Functional studies in a mutant cell line (Ka13) expressing neither HIF-1α nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPAS-1 transactivation (relative to HIF-1α transactivation) of the VEGF promoter than the LDH-A promoter.

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