Identification and localization of a sea urchin Notch homologue: insights into vegetal plate regionalization and Notch receptor regulation

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3363-3374 ◽  
Author(s):  
D.R. Sherwood ◽  
D.R. McClay
Keyword(s):  
Sea Urchin ◽  
Basolateral Membrane ◽  
Notch Pathway ◽  
Cell Types ◽  
Dorsal Side ◽  
Notch Receptor ◽  
Molecular Organization ◽  
Intercellular Signaling ◽  
Vegetal Pole ◽  
Numerous Cell

The specifications of cell types and germ-layers that arise from the vegetal plate of the sea urchin embryo are thought to be regulated by cell-cell interactions, the molecular basis of which are unknown. The Notch intercellular signaling pathway mediates the specification of numerous cell fates in both invertebrate and vertebrate development. To gain insights into mechanisms underlying the diversification of vegetal plate cell types, we have identified and made antibodies to a sea urchin homolog of Notch (LvNotch). We show that in the early blastula embryo, LvNotch is absent from the vegetal pole and concentrated in basolateral membranes of cells in the animal half of the embryo. However, in the mesenchyme blastula embryo LvNotch shifts strikingly in subcellular localization into a ring of cells which surround the central vegetal plate. This ring of LvNotch delineates a boundary between the presumptive secondary mesoderm and presumptive endoderm, and has an asymmetric bias towards the dorsal side of the vegetal plate. Experimental perturbations and quantitative analysis of LvNotch expression demonstrate that the mesenchyme blastula vegetal plate contains both animal/vegetal and dorsoventral molecular organization even before this territory invaginates to form the archenteron. Furthermore, these experiments suggest roles for the Notch pathway in secondary mesoderm and endoderm lineage segregation, and in the establishment of dorsoventral polarity in the endoderm. Finally, the specific and differential subcellular expression of LvNotch in apical and basolateral membrane domains provides compelling evidence that changes in membrane domain localization of LvNotch are an important aspect of Notch receptor function.

A micromere induction signal is activated by beta-catenin and acts through notch to initiate specification of secondary mesenchyme cells in the sea urchin embryo

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5113-5122 ◽  
Author(s):  
D.R. McClay ◽  
R.E. Peterson ◽  
R.C. Range ◽  
A.M. Winter-Vann ◽  
M.J. Ferkowicz
Keyword(s):  
Sea Urchin ◽  
Notch Pathway ◽  
Notch Receptor ◽  
Cell Diameter ◽  
Beta Catenin ◽  
Animal Pole ◽  
Induction Signal ◽  
Vegetal Pole ◽  
Mesenchyme Cells ◽  
To Receive

At fourth cleavage of sea urchin embryos four micromeres at the vegetal pole separate from four macromeres just above them in an unequal cleavage. The micromeres have the capacity to induce a second axis if transplanted to the animal pole and the absence of micromeres at the vegetal pole results in the failure of macromere progeny to specify secondary mesenchyme cells (SMCs). This suggests that micromeres have the capacity to induce SMCs. We demonstrate that micromeres require nuclear beta-catenin to exhibit SMC induction activity. Transplantation studies show that much of the vegetal hemisphere is competent to receive the induction signal. The micromeres induce SMCs, most likely through direct contact with macromere progeny, or at most a cell diameter away. The induction is quantitative in that more SMCs are induced by four micromeres than by one. Temporal studies show that the induction signal is passed from the micromeres to macromere progeny between the eighth and tenth cleavage. If micromeres are removed from hosts at the fourth cleavage, SMC induction in hosts is rescued if they later receive transplanted micromeres between the eighth and tenth cleavage. After the tenth cleavage addition of induction-competent micromeres to micromereless embryos fails to specify SMCs. For macromere progeny to be competent to receive the micromere induction signal, beta-catenin must enter macromere nuclei. The macromere progeny receive the micromere induction signal through the Notch receptor. Signaling-competent micromeres fail to induce SMCs if macromeres express dominant-negative Notch. Expression of an activated Notch construct in macromeres rescues SMC specification in the absence of induction-competent micromeres. These data are consistent with a model whereby beta-catenin enters the nuclei of micromeres and, as a consequence, the micromeres produce an inductive ligand. Between the eighth and tenth cleavage micromeres induce SMCs through Notch. In order to be receptive to the micromere inductive signal the macromeres first must transport beta-catenin to their nuclei, and as one consequence the Notch pathway becomes competent to receive the micromere induction signal, and to transduce that signal. As Notch is maternally expressed in macromeres, additional components must be downstream of nuclear beta-catenin in macromeres for these cells to receive and transduce the micromere induction signal.

LvNotch signaling mediates secondary mesenchyme specification in the sea urchin embryo

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1703-1713 ◽  
Author(s):  
D.R. Sherwood ◽  
D.R. McClay
Keyword(s):  
Sea Urchin ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Notch Receptor ◽  
Dominant Negative ◽  
Sea Urchin Embryo ◽  
Numerous Cell ◽  
Vertebrate Embryos ◽  
Mesenchyme Cells ◽  
Molecular Bases

Cell-cell interactions are thought to regulate the differential specification of secondary mesenchyme cells (SMCs) and endoderm in the sea urchin embryo. The molecular bases of these interactions, however, are unknown. We have previously shown that the sea urchin homologue of the LIN-12/Notch receptor, LvNotch, displays dynamic patterns of expression within both the presumptive SMCs and endoderm during the blastula stage, the time at which these two cell types are thought to be differentially specified (Sherwood, D. R. and McClay, D. R. (1997) Development 124, 3363–3374). The LIN-12/Notch signaling pathway has been shown to mediate the segregation of numerous cell types in both invertebrate and vertebrate embryos. To directly examine whether LvNotch signaling has a role in the differential specification of SMCs and endoderm, we have overexpressed activated and dominant negative forms of LvNotch during early sea urchin development. We show that activation of LvNotch signaling increases SMC specification, while loss or reduction of LvNotch signaling eliminates or significantly decreases SMC specification. Furthermore, results from a mosaic analysis of LvNotch function as well as endogenous LvNotch expression strongly suggest that LvNotch signaling acts autonomously within the presumptive SMCs to mediate SMC specification. Finally, we demonstrate that the expansion of SMCs seen with activation of LvNotch signaling comes at the expense of presumptive endoderm cells, while loss of SMC specification results in the endoderm expanding into territory where SMCs usually arise. Taken together, these results offer compelling evidence that LvNotch signaling directly specifies the SMC fate, and that this signaling is critical for the differential specification of SMCs and endoderm in the sea urchin embryo.

Bi-Directional Notch Signaling Via Signal-Sending and Signal-Receiving Microdomains of the Partnered Immunological Synapses during Th:DC Interaction.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 646-646
Author(s):  
Yatin M. Vyas ◽  
Jerome Parness ◽  
David Rodeberg ◽  
Winifred Huang
Keyword(s):  
Immune Responses ◽  
Notch Signaling ◽  
Information Transfer ◽  
Notch Pathway ◽  
Signal Propagation ◽  
Cell Types ◽  
Notch Receptor ◽  
Cell Fate Decisions ◽  
Notch Ligands ◽  
Notch1 Receptor

Abstract The Notch pathway regulates adaptive immune responses, yet the temporal development of a specific molecular anatomy underlying the directionality of Notch signaling, central to cell-fate decisions, remains unknown. Using the development of the functional immune synapse (IS) of the human physiological T-helper lymphocyte (Th): Dendritic cell (DC) interaction as our model, we followed the temporal accumulation of Notch signaling components, unprocessed and processed, in the developing ThIS and the apposed DCIS of these cells by 2D and 3D immunofluorescense microscopy. Downstream Notch targets in both cell types were followed, as well. We demonstrate that Th-Notch1 receptor and DC-Notch ligands (Delta-like1, Jagged-1) cluster in their apposed central-supramolecular-activation-clusters (cSMAC), whereas DC-Notch1 receptor and Th-Notch ligands cluster in their apposed peripheral-SMAC in an anti-parallel arrangement to that seen in the cSMAC. The resultant accumulation in both cell types of processed nuclear Notch receptor, its ligands, as well as HES-1 and phosphorylated-STAT3, supports antiparallel, reciprocal Notch signal propagation in the DC-to-Th direction via the cSMAC and Th-to-DC direction via the pSMAC. The imposed asymmetric recruitment of the components of Notch pathway, therefore, provides a novel bi-directional route by which the partnered ThIS and DCIS regulate Notch-mediated immune responses. Our data indicate that terminally differentiated immune cells communicate bidirectionally using unidirectional Notch signaling platforms that are spatially segregated into reciprocally signaling microdomains. Significantly, our observations of bidirectional Notch signaling indicate that the heterologous Th:DC interaction is cooperative, requiring reciprocal information transfer across both cell types to mount an appropriate immune response.

The role of micromere signaling in Notch activation and mesoderm specification during sea urchin embryogenesis

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5255-5265 ◽  
Author(s):  
H.C. Sweet ◽  
P.G. Hodor ◽  
C.A. Ettensohn
Keyword(s):  
Notch Signaling ◽  
Sea Urchin ◽  
Muscle Cells ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Notch Receptor ◽  
Pigment Cells ◽  
Animal Cells ◽  
Mesodermal Cell ◽  
Mesoderm Development

In the sea urchin embryo, the micromeres act as a vegetal signaling center. These cells have been shown to induce endoderm; however, their role in mesoderm development has been less clear. We demonstrate that the micromeres play an important role in the induction of secondary mesenchyme cells (SMCs), possibly by activating the Notch signaling pathway. After removing the micromeres, we observed a significant delay in the formation of all mesodermal cell types examined. In addition, there was a marked reduction in the numbers of pigment cells, blastocoelar cells and cells expressing the SMC1 antigen, a marker for prospective SMCs. The development of skeletogenic cells and muscle cells, however, was not severely affected. Transplantation of micromeres to animal cells resulted in the induction of SMC1-positive cells, pigment cells, blastocoelar cells and muscle cells. The numbers of these cell types were less than those found in sham transplantation control embryos, suggesting that animal cells are less responsive to the micromere-derived signal than vegetal cells. Previous studies have demonstrated a role for Notch signaling in the development of SMCs. We show that the micromere-derived signal is necessary for the downregulation of the Notch protein, which is correlated with its activation, in prospective SMCs. We propose that the micromeres induce adjacent cells to form SMCs, possibly by presenting a ligand for the Notch receptor.

LvDelta is a mesoderm-inducing signal in the sea urchin embryo and can endow blastomeres with organizer-like properties

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1945-1955 ◽  
Author(s):  
Hyla C. Sweet ◽  
Michael Gehring ◽  
Charles A. Ettensohn
Keyword(s):  
Sea Urchin ◽  
Critical Role ◽  
Cell Types ◽  
Notch Signaling Pathway ◽  
Notch Receptor ◽  
Pigment Cells ◽  
Mesodermal Cell ◽  
Sea Urchin Embryo ◽  
Organizing Center ◽  
Necessary And Sufficient

Signals from micromere descendants play a critical role in patterning the early sea urchin embryo. Previous work demonstrated a link between the induction of mesoderm by micromere descendants and the Notch signaling pathway. In this study, we demonstrate that these micromere descendants express LvDelta, a ligand for the Notch receptor. LvDelta is expressed by micromere descendants during the blastula stage, a time when signaling has been shown to occur. By a combination of embryo microsurgery, mRNA injection and antisense morpholino experiments, we show that expression of LvDelta by micromere descendants is both necessary and sufficient for the development of two mesodermal cell types, pigment cells and blastocoelar cells. We also demonstrate that LvDelta is expressed by macromere descendants during mesenchyme blastula and early gastrula stages. Macromere-derived LvDelta is necessary for blastocoelar cell and muscle cell development. Finally, we find that expression of LvDelta is sufficient to endow blastomeres with the ability to function as a vegetal organizing center and to coordinate the development of a complete pluteus larva.

scholarly journals Noncanonical Notch signals have opposing roles during cardiac development

2021 ◽  
Author(s):  
Matthew Miyamoto ◽  
Peter Andersen ◽  
Edrick Sulistio ◽  
Xihe Liu ◽  
Sean Murphy ◽  
...  
Keyword(s):  
Cell Fate ◽  
Heart Development ◽  
Cardiac Development ◽  
Embryonic Stem ◽  
Notch Pathway ◽  
Intercellular Signaling ◽  
Numerous Cell ◽  
Notch Cleavage ◽  
Fate Decision

The Notch pathway is an ancient intercellular signaling system with crucial roles in numerous cell-fate decision processes across species. While the canonical pathway is activated by ligand-induced cleavage and nuclear localization of membrane-bound Notch, Notch can also exert its activity in a ligand/transcription-independent fash- ion, which is conserved in Drosophila, Xenopus, and mammals. How- ever, the noncanonical role remains poorly understood in in vivo pro- cesses. Here we show that increased levels of the Notch intracellular domain (NICD) in the early mesoderm inhibit heart development, po- tentially through impaired induction of the second heart field (SHF), independently of the transcriptional effector RBP-J. Similarly, inhibit- ing Notch cleavage, shown to increase noncanonical Notch activ- ity, suppressed SHF induction in embryonic stem cell (ESC)-derived mesodermal cells. In contrast, NICD overexpression in late cardiac progenitor cells lacking RBP-J resulted in an increase in heart size. Our study suggests that noncanonical Notch signaling has stage- specific roles during cardiac development.

scholarly journals Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 521
Author(s):  
Catia Giovannini ◽  
Francesca Fornari ◽  
Fabio Piscaglia ◽  
Laura Gramantieri
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Hepatitis Virus ◽  
Notch Pathway ◽  
Notch Receptor ◽  
Gamma Secretase ◽  
Stem Cell Maintenance ◽  
Pathway Activation ◽  
Promising Therapeutic Approach ◽  
Conserved Genes

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.

scholarly journals Single-cell transcriptomics following ischemic injury identifies a role for B2M in cardiac repair

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bas Molenaar ◽  
Louk T. Timmer ◽  
Marjolein Droog ◽  
Ilaria Perini ◽  
Danielle Versteeg ◽  
...  
Keyword(s):  
Single Cell ◽  
Communication Networks ◽  
Cardiac Remodeling ◽  
Cardiac Injury ◽  
Ischemic Injury ◽  
Cell Types ◽  
Repair Process ◽  
Cardiac Repair ◽  
Cellular Heterogeneity ◽  
Intercellular Signaling

AbstractThe efficiency of the repair process following ischemic cardiac injury is a crucial determinant for the progression into heart failure and is controlled by both intra- and intercellular signaling within the heart. An enhanced understanding of this complex interplay will enable better exploitation of these mechanisms for therapeutic use. We used single-cell transcriptomics to collect gene expression data of all main cardiac cell types at different time-points after ischemic injury. These data unveiled cellular and transcriptional heterogeneity and changes in cellular function during cardiac remodeling. Furthermore, we established potential intercellular communication networks after ischemic injury. Follow up experiments confirmed that cardiomyocytes express and secrete elevated levels of beta-2 microglobulin in response to ischemic damage, which can activate fibroblasts in a paracrine manner. Collectively, our data indicate phase-specific changes in cellular heterogeneity during different stages of cardiac remodeling and allow for the identification of therapeutic targets relevant for cardiac repair.

scholarly journals Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

2020 ◽  
Vol 21 (24) ◽  
pp. 9585
Author(s):  
Melania Dovizio ◽  
Patrizia Ballerini ◽  
Rosa Fullone ◽  
Stefania Tacconelli ◽  
Annalisa Contursi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Cell Communication ◽  
Antiplatelet Agents ◽  
Cell Types ◽  
Disease Monitoring ◽  
Crucial Component ◽  
Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

scholarly journals Functional Gap Junctions in the Early Sea Urchin Embryo Are Localized to the Vegetal Pole

1999 ◽  
Vol 212 (2) ◽  
pp. 503-510 ◽  
Author(s):  
Ikuko Yazaki ◽  
Brian Dale ◽  
Elisabetta Tosti
Keyword(s):  
Gap Junctions ◽  
Sea Urchin ◽  
Sea Urchin Embryo ◽  
Vegetal Pole
Sign in / Sign up

Export Citation Format

Share Document