scholarly journals A combination of notch signaling, preferential adhesion and endocytosis induces a slow mode of cell intercalation in the Drosophila retina

Development ◽  
2021 ◽  
Author(s):  
Laura Blackie ◽  
Melda Tozluoglu ◽  
Mateusz Trylinski ◽  
Rhian F. Walther ◽  
François Schweisguth ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Slow Mode ◽  
Cone Cells ◽  
Long Time ◽  
Fly Eye ◽  
Cell Intercalation ◽  
Actomyosin Cytoskeleton ◽  
Different Cell Types

Movement of epithelial cells in a tissue occurs through neighbor exchange and drives tissue shape changes. It requires intercellular junction remodeling, a process typically powered by the contractile actomyosin cytoskeleton. This has mostly been investigated in homogeneous epithelia where intercalation takes minutes. However, in some tissues, intercalation involves different cell types and can take hours. Whether slow and fast intercalation share the same mechanisms remains to be examined. To address this issue, we use the fly eye, where the cone cells exchange neighbors over approximately 10 hours to shape the lens. We uncover three pathways regulating this slow mode of cell intercalation. Firstly, we find a limited requirement for MyosinII. In this case, mathematical modeling predicts an adhesion dominant intercalation mechanism. Genetic experiments support this prediction and reveal a role for adhesion through the Nephrin proteins Roughest and Hibris. Secondly, we find cone cell intercalation is regulated by the Notch-signaling pathway. Thirdly, we show endocytosis is required for membrane removal and Notch activation. Altogether, our work indicates that adhesion, endocytosis and Notch can induce junction remodeling over long-time scales.

scholarly journals Neph/Nephrin-like adhesion and tissue level pulling forces regulate cell intercalation during Drosophila retina development

2019 ◽  
Author(s):  
Laura Blackie ◽  
Melda Tozluoglu ◽  
Mateusz Trylinski ◽  
Rhian F. Walther ◽  
Yanlan Mao ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Tissue Level ◽  
Notch Signaling Pathway ◽  
Pigment Cells ◽  
Retina Development ◽  
Cone Cells ◽  
Pulling Forces ◽  
Cell Intercalation ◽  
Actomyosin Cytoskeleton ◽  
Cell Adhesion Proteins

SUMMARYIntercalation between neighboring cells contributes to shaping epithelial tissues and is regulated by the contractile actomyosin cytoskeleton. While intercalation typically occurs over minutes, instances of much slower cell intercalation have been reported during organogenesis. This is observed, for example, for the four glial-like cone cells (CC) that intercalate during Drosophila retinal patterning. Here we show that Myosin-II activity in the CCs is largely dispensable for their intercalation. Instead, we find that differential activity of the Notch-signaling pathway within the CC quartet regulates intercalation, which also depends on the cell adhesion proteins Roughest and Hibris. In addition, mathematical modeling predicts that forces external to the intercalating CC quartet are necessary for intercalation. Consistent with this prediction we show that the surrounding primary pigment cells are under significant contractile tension. Altogether, our work elucidates a novel mode of cell intercalation that relies on Neph/Nephrin-like adhesion and forces external to the intercalating cells.

scholarly journals High-precision 3D inkjet technology for live cell bioprinting

2019 ◽  
Vol 5 (2) ◽  
pp. 27 ◽  
Author(s):  
Daisuke Takagi ◽  
Waka Lin ◽  
Takahiko Matsumoto ◽  
Hidekazu Yaginuma ◽  
Natsuko Hemmi ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Cell Number ◽  
Live Cell ◽  
Drop On Demand ◽  
Long Time ◽  
Spatial Positioning ◽  
Different Cell Types ◽  
Membrane Vibrations

In recent years, bioprinting has emerged as a promising technology for the construction of three-dimensional (3D) tissues to be used in regenerative medicine or in vitro screening applications. In the present study, we present the development of an inkjet-based bioprinting system to arrange multiple cells and materials precisely into structurally organized constructs. A novel inkjet printhead has been specially designed for live cell ejection. Droplet formation is powered by piezoelectric membrane vibrations coupled with mixing movements to prevent cell sedimentation at the nozzle. Stable drop-on-demand dispensing and cell viability were validated over an adequately long time to allow the fabrication of 3D tissues. Reliable control of cell number and spatial positioning was demonstrated using two separate suspensions with different cell types printed sequentially. Finally, a process for constructing stratified Mille-Feuille-like 3D structures is proposed by alternately superimposing cell suspensions and hydrogel layers with a controlled vertical resolution. The results show that inkjet technology is effective for both two-dimensional patterning and 3D multilayering and has the potential to facilitate the achievement of live cell bioprinting with an unprecedented level of precision.

MP41-03 NOTCH SIGNALING PATHWAY AS COMMON TARGET OF ERG IN DIVERSE TUMOR CELL TYPES

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Ahmed Mohamed ◽  
Lakshmi Ravindranath ◽  
Shilpa Katta ◽  
Shyh-Han Tan ◽  
Yongmei Chen ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Common Target

scholarly journals Multifaceted regulation of Notch signaling by glycosylation

Glycobiology ◽  
2020 ◽  
Author(s):  
Ashutosh Pandey ◽  
Nima Niknejad ◽  
Hamed Jafar-Nejad
Keyword(s):  
Notch Signaling ◽  
Cell Biology ◽  
Normal Development ◽  
Notch Pathway ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Protein Glycosylation ◽  
Notch Receptors ◽  
Current Review ◽  
Notch Activation

Abstract To build a complex body composed of various cell types and tissues and to maintain tissue homeostasis in the postembryonic period, animals use a small number of highly conserved intercellular communication pathways. Among these is the Notch signaling pathway, which is mediated via the interaction of transmembrane Notch receptors and ligands usually expressed by neighboring cells. Maintaining optimal Notch pathway activity is essential for normal development, as evidenced by various human diseases caused by decreased and increased Notch signaling. It is therefore not surprising that multiple mechanisms are used to control the activation of this pathway in time and space. Over the last 20 years, protein glycosylation has been recognized as a major regulatory mechanism for Notch signaling. In this review, we will provide a summary of the various types of glycan that have been shown to modulate Notch signaling. Building on recent advances in the biochemistry, structural biology, cell biology and genetics of Notch receptors and the glycosyltransferases that modify them, we will provide a detailed discussion on how various steps during Notch activation are regulated by glycans. Our hope is that the current review article will stimulate additional research in the field of Notch glycobiology and will potentially be of benefit to investigators examining the contribution of glycosylation to other developmental processes.

scholarly journals The Tuberculous Granuloma: An Unsuccessful Host Defence Mechanism Providing a Safety Shelter for the Bacteria?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mayra Silva Miranda ◽  
Adrien Breiman ◽  
Sophie Allain ◽  
Florence Deknuydt ◽  
Frederic Altare
Keyword(s):  
Cell Types ◽  
Giant Cells ◽  
The Body ◽  
Differentiated Cells ◽  
Latently Infected ◽  
Long Time ◽  
Infectious Stage ◽  
Different Cell Types

One of the main features of the immune response toM. Tuberculosisis the formation of an organized structure called granuloma. It consists mainly in the recruitment at the infectious stage of macrophages, highly differentiated cells such as multinucleated giant cells, epithelioid cells and Foamy cells, all these cells being surrounded by a rim of lymphocytes. Although in the first instance the granuloma acts to constrain the infection, some bacilli can actually survive inside these structures for a long time in a dormant state. For some reasons, which are still unclear, the bacilli will reactivate in 10% of the latently infected individuals, escape the granuloma and spread throughout the body, thus giving rise to clinical disease, and are finally disseminated throughout the environment. In this review we examine the process leading to the formation of the granulomatous structures and the different cell types that have been shown to be part of this inflammatory reaction. We also discuss the differentin vivoandin vitromodels available to study this fascinating immune structure.

Delta-Notch signaling induces hypochord development in zebrafish

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2555-2563 ◽  
Author(s):  
Andrew J. Latimer ◽  
Xinhong Dong ◽  
Youlia Markov ◽  
Bruce Appel
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Cell Types ◽  
Paraxial Mesoderm ◽  
Loss Of Function ◽  
Cell Type ◽  
No Tail ◽  
Vertebrate Embryos ◽  
Different Cell Types ◽  
Her4 Expression

Different cell types that occupy the midline of vertebrate embryos originate within the Spemann-Mangold or gastrula organizer. One such cell type is hypochord, which lies ventral to notochord in anamniote embryos. We show that hypochord precursors arise from the lateral edges of the organizer in zebrafish. During gastrulation, hypochord precursors are closely associated with no tail-expressing midline precursors and paraxial mesoderm, which expresses deltaC and deltaD. Loss-of-function experiments revealed that deltaC and deltaD were required for her4 expression in presumptive hypochord precursors and for hypochord development. Conversely, ectopic, unregulated Notch activity blocked no tail expression and promoted her4 expression. We propose that Delta signaling from paraxial mesoderm diversifies midline cell fate by inducing a subset of neighboring midline precursors to develop as hypochord, rather than as notochord.

scholarly journals Abnormally localized DLK1 interacts with NCOR1 in non-small cell lung cancer cell nuclear

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Jinjing Tan ◽  
Susu Zhang ◽  
Lin Li ◽  
Jing Mu ◽  
Ziyu Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Signaling Activation ◽  
Different Cell Types

Abstract Delta-like homolog 1 (DLK1) regulates noncanonical Notch signaling pathway as ligand. DLK1 was abnormally expressed in a variety of tumors, affecting tumorigenesis and developments. The biological function of DLK1 toward cell proliferation and signaling activation was controversial across different cell types. Two currently known isoforms of DLK1, which are membrane-tethered isoform and soluble isoform, are believed to be the key of DLK1 dual behaviors. While these isoforms are not enough to explain the phenomena, our observations offer the possibility of a third isoform of DLK1. In the present study, we verified the nuclear localization of DLK1 in lung cancer cells. The nuclear localized DLK1 was observed in 107 of 351 non-small cell lung cancer (NSCLC) samples and was associated with tissue differentiation and tumor size. Through co-immunoprecipitation (co-IP) combined mass spectrometry (MS), we identified nuclear receptor corepressor 1 (NCOR1) as DLK1’s novel interaction protein and confirmed their interaction in nuclear. We analyzed the expression of NCOR1 in two independent cohorts and demonstrated that NCOR1 is a tumor suppressor and has prognosis potential in lung squamous carcinomas. At last, we analyzed the colocalization of DLK1 and NCOR1 in 147 NSCLC samples by immunohistochemistry (IHC). The result indicated NCOR1 might participate with nuclear localized DLK1 in regulating cell differentiation.

scholarly journals Cis-activation in the Notch signaling pathway

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Nagarajan Nandagopal ◽  
Leah A Santat ◽  
Michael B Elowitz
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Single Cells ◽  
Notch Pathway ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Activation Process ◽  
Additional Mode ◽  
Ligand Expression ◽  
Multiple Ligand

The Notch signaling pathway consists of transmembrane ligands and receptors that can interact both within the same cell (cis) and across cell boundaries (trans). Previous work has shown that cis-interactions act to inhibit productive signaling. Here, by analyzing Notch activation in single cells while controlling cell density and ligand expression level, we show that cis-ligands can also activate Notch receptors. This cis-activation process resembles trans-activation in its ligand level dependence, susceptibility to cis-inhibition, and sensitivity to Fringe modification. Cis-activation occurred for multiple ligand-receptor pairs, in diverse cell types, and affected survival in neural stem cells. Finally, mathematical modeling shows how cis-activation could potentially expand the capabilities of Notch signaling, for example enabling ‘negative’ (repressive) signaling. These results establish cis-activation as an additional mode of signaling in the Notch pathway, and should contribute to a more complete understanding of how Notch signaling functions in developmental, physiological, and biomedical contexts.

The ultra-structure of the developing eye of Drosophila

1960 ◽  
Vol 153 (951) ◽  
pp. 155-178 ◽  
Keyword(s):  
Nuclear Envelope ◽  
Cell Types ◽  
Pigment Cells ◽  
Cell Organelles ◽  
Ultra Structure ◽  
Cell Structures ◽  
Cone Cells ◽  
Different Types ◽  
Different Cell Types ◽  
First Time

A description is given of the ultra-structure of the eye of Drosophila melanogaster during its development from the imaginal bud of the late larva till it attains its final form in the adult. Six markedly different types of cells develop out of the apparently uniform epithelium of the imaginal bud; namely, cone cells, retinula cells, primary pigment cells, secondary and basal pigment cells, two [inner and outer] types of hair-nerve cells. In each type of cell there is a characteristic form of cytoplasmic double-membrane structure [endoplasmic reticulum] which reaches its highest development at or just before the time at which the characteristic cell structures are being formed. In most types of cell there are indications of the participation of the nucleus, or nuclear envelope, in cell differentiation, these indications being different in the different cell types. In retinula cells and also in inner hairnerve cells there is evidence suggesting that the outer layer of the nuclear envelope may give rise directly to cytoplasmic double membranes. Several cell organelles are described for the first time, in particular the rhabdomere vesicular spheroids and the cone cell granules. In the formation of the rhabdomeres by the retinula cells, the first stages in the deposition of this structure are carried out by the plasma membrane on the cells. The presence of an eighth retinula is confirmed. The implications of the observations for our general understanding of cell activities during differentiation is briefly discussed; work already in progress with various mutants is expected to reveal new facts of interest in this connexion.

scholarly journals Notch signaling: switching an oncogene to a tumor suppressor

Blood ◽  
2014 ◽  
Vol 123 (16) ◽  
pp. 2451-2459 ◽  
Author(s):  
Camille Lobry ◽  
Philmo Oh ◽  
Marc R. Mansour ◽  
A. Thomas Look ◽  
Iannis Aifantis
Keyword(s):  
Tumor Suppressor ◽  
Notch Signaling ◽  
Cell Fate ◽  
Lymphoblastic Leukemia ◽  
Cell Types ◽  
Hematologic Malignancies ◽  
Notch Signaling Pathway ◽  
Lymphocytic Leukemia ◽  
Splenic Marginal Zone Lymphoma ◽  
Cell Fate Determinant

Abstract The Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types. Notch is a binary cell-fate determinant, and its hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Recently, several studies also unraveled tumor-suppressor roles for Notch signaling in different tissues, including tissues where it was before recognized as an oncogene in specific lineages. Whereas involvement of Notch as an oncogene in several lymphoid malignancies (T-ALL, B-chronic lymphocytic leukemia, splenic marginal zone lymphoma) is well characterized, there is growing evidence involving Notch signaling as a tumor suppressor in myeloid malignancies. It therefore appears that Notch signaling pathway’s oncogenic or tumor-suppressor abilities are highly context dependent. In this review, we summarize and discuss latest advances in the understanding of this dual role in hematopoiesis and the possible consequences for the treatment of hematologic malignancies.

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