1) Does Notch Delta interact at new adherens junction interface formed between the two sister cells?
There is evidence in vertebrates developing brains that Notch activation occurs at the level of adherens junction and it is restricted to the two sister cells after division. Our preliminary observations that sister cells share a stable new adherens junctions interface suggests that Notch Delta interactions may occur at this place. To test whether Notch Delta interact at new adherens junction formed between the two sister cells we will first assess whether Notch receptor is activated in this region. For that we will express Notch receptor 1a and 1b tagged with photoconvertible fluorescent protein Dendra as previously described in drosophila: and mouse: . We will photoconvert Notch Dendra at new adherens junction interface and trace the nuclear translocation of Notch intracellular domain. Accordingly to our initial hypothesis Notch1-Dendra photoconverted at the new adherens junction interface but not elsewhere will translocate to the nucleus. Adherens junction will be labeled by Par3-GFP or –CFP and new adherens junction interface will be monitored by live-imaging as shown in fig..
To complement these experiments we will determine whether Delta Notch interact at new adherens junctions interface by tagging Notch ligands (zDelta 1, 2 and 3) and receptors with non-fluorescent split-GFP fragments (GFP exons- 1-10 and GFP exon 11) (ref). We predict that once Delta and Notch
Numerous cells have little, finger-formed projections of the plasma film on their uncovered surfaces. These projections, called microvilli (solitary, microvillus), significantly increment the surface territory of the phone presented to the extracellular environment. Likewise, they cover the surfaces of cells that are effectively engrossing materials from the extracellular liquid, for example, the cells coating the stomach related tract. Microvilli have broad associations with the cytoskeleton. A center of small scale fibers hardens each microvillus and grapples it to the cytoskeleton at the terminal web.
Which of the following structures is not normally found in the cytoplasm of a resting cell?
Brennan K, Tateson R, Lewis K, Arias AM. A Functional Analysis of Notch Mutations in Drosophila. Genetics. 1997;147(1):177-188.
Epithelial-mesenchymal transition (EMT) is a cellular process that is essential for normal processes in many organisms, including embryonic development and wound healing, and is recapitulated in human disease, contributing to organ fibrosis and cancer progression (Thiery et al. 2009; Yang and Weinberg 2008). EMT describes the conversion of a cell with an epithelial phenotype to one with mesenchymal characteristics and can be a partial or complete transformation. Epithelial cells form the borders of tissues and organs, and are characterized by apical-basal polarity, contact with a basement membrane, and strong adherence to other epithelial cells through intercellular junctions including adherens junctions, tight junctions, and desmosomes. Conversely, mesenchymal cells have front-rear polarity and generally lack cell-cell contact, allowing them to be motile. During human embryonic development, EMT is essential for the formation of a variety of tissues, including mesoderm, neural crest, somites, palate, pancreas, liver, reproductive tracts, and heart valves (Thiery et al. 2009; Yang and Weinberg 2008). After development, partial EMT also contributes to wound healing (Thiery et al. 2009). However, EMT can also play a more insidious role by factoring into tumour progression.
• Very little intercellular space between cells TYPES OF EPITHELIUM SHAPE 1. Squamous 2.
Figure 1.b shows the ‘Lock and Key’ model where two individual substrates meet the active site where
I think the cell from NPC would look like clusters of bumps attacking the smooth Endoplasmic Reticulum
The expression of Notch1 and Notch2 in HSCs is shown to be important for their response to endothelial – derived maintenance factor.
How are medially-positioned progenitors affected by diffusible signals? The number of neurons belonging to populations found near or at the centre of the dorsoventral axis of the cord is influenced by signal levels, including Shh and BMPs. A moderate concentration of BMP signaling is needed to generate the correct number of medial interneurons. In zebrafish mutants in which a particular BMP protein is functionally reduced, there was a resulting increase in Lim1+ interneurons (medial interneurons) post-mitotically (Nguyen et al., 2000). Interestingly, further BMP reduction decreases medial interneuron counts, illustrating the fine balance of BMP levels that is needed to establish appropriate medial interneuron expression. Perturbing natural
GnT-III suppression alters Notch receptor localization- Autophagy has been shown to regulate the Notch pathway in normal physiology and disease (16). Therefore we performed immunocytochemistry to determine the localization of Notch 1 in OVCAR3 cells. Notch 1 is observed in intracellular vesicles and the nucleus in control shRNA OVCAR3 cells and does not colocalize with LAMP1 (Fig. 5A). However, in GnT-III shRNA OVCAR3 cells Notch 1 is primarily localized with the late endosome/lysosome marker LAMP1 indicating that a larger percentage of Notch 1 is in this fraction (Fig. 5A, white arrows). To further confirm these findings we treated cells with chloroquine to raise the pH of this cellular compartment and inhibit lysosomal enzymes (17). We found no effect on Notch 1 levels in control cells treated with chloroquine; while GnT-III shRNA cells show a significant increase in Notch 1 levels when lysosomal enzymes are inhibited (Fig. 5B).
If my hypothesis is supported, the images of PKCγ-Cγ1 will show the PKCγ spread towards the edges of the cell and be less concentrated in the middle. The images of fascin-FTIC will show that the fascin has moved toward the edges of the cell along with the PKCγ. Layered images will show the overlapping of of PKCγ and fascin, suggesting a strong interaction between the two proteins. A magnified inspection of the edges of the cell will show both PKCγ and fascin have concentrated in the protrusions of the cell
Mutations in genes coding for component of the Notch signaling pathway cause a disease called Alagille syndrome. Alagille syndrome (ALGS) is a multi-organ pediatric disorder. Some ALGS patients develop small multi-cystic kidney disease. The Surendran lab has developed mouse models of Notch-signaling-deficient multicystic kidney disease. Studies in the mouse models have revealed that Notch signaling “maintains the alignment of cell division in the proximal tubules during nephrogenesis and loss of Notch signaling may lead to cystic renal disease and tumorigenesis due to misoriented cell division” (Surendran, Selassie, Liapis, Krigman, Kopan, 2010). Notch Signaling occurs between neighboring cells, in which ligand expressing cell activate the
The five different cell junctions are known as tight, gap, desmosome, hemidesmosome and adherens junctions.
connecting cilium between the outer segment and the cell body in rod and cone cell is a