scholarly journals MYC activity is required for maintenance of the Neuromesodermal Progenitor signalling network and for correct timing of segmentation clock gene oscillations

2017 ◽  
Author(s):  
Ioanna Mastromina ◽  
Laure Verrier ◽  
Kate G. Storey ◽  
J. Kim Dale

AbstractThe Myc transcriptional regulators are implicated in a range of cellular functions, including proliferation, cell cycle progression, metabolism and pluripotency maintenance. Here, we investigated the expression, regulation and function of Myc during mouse embryonic axis elongation and segmentation. Expression of both cMyc and MycN in the domains where neuromesodermal progenitors (NMPs) and underlying caudal pre-somitic mesoderm (cPSM) cells reside is coincident WNT and FGF signals; factors known to maintain progenitors in an undifferentiated state. Pharmacological inhibition of MYC activity, downregulates expression of WNT/FGF components. In turn, we find that cMyc expression is WNT, FGF and NOTCH regulated, placing it centrally in the signalling circuit that operates in the tail end that both sustains progenitors and drives maturation of the PSM into somites. Interfering with MYC function in the PSM, where it displays oscillatory expression, delays the timing of segmentation clock oscillations and thus of somite formation. In summary, we identify Myc as a component that links NMP maintenance and PSM maturation during the body axis elongation stages of mouse embryogenesis.Summary StatementMYC operates in a positive feedback loop with WNT/FGF signals to maintain the progenitors which facilitate body axis elongation while its activity is crucial for timing of the segmentation clock.

‘Cellular structure and function’ covers the roles, structures, and functions of the main four types of macromolecules of the human body, namely proteins, lipids, carbohydrates, and nucleic acids. For these macromolecules, the roles and types of each class are discussed (for proteins this includes their roles as structural proteins and enzymes and their kinetics; for lipids, the roles and types of lipid found in the body are considered; for carbohydrates, their roles including structural and metabolic are discussed; and the structure of nucleic acids is described). Then follows a description of the organization of the cell, including the plasma membrane and its components, and the intracellular organelles. Cell growth, division, and apoptosis are covered, as are the formation of gametes, and finally the principles of how cellular functions can be modulated by pharmacological agents through receptors and signalling pathways are discussed.


2015 ◽  
Author(s):  
Benjamin Steventon ◽  
Fernando Duarte ◽  
Ronan Lagadec ◽  
Sylvie Mazan ◽  
Jean-Fran&ccedilois Nicolas ◽  
...  

Axial elongation is a widespread mechanism propelling the generation of the metazoan body plan. A widely accepted model is that of posterior growth, where new tissue is continually added from the posterior unsegmented tip of the body axis. A key question is whether or not such a posterior growth zone generates sufficient additional tissue volume to generate elongation of the body axis, and the degree to which this is balanced with tissue convergence and/or growth in already segmented regions of the body axis. We applied a multi-scalar morphometric analysis during posterior axis elongation in zebrafish. Importantly, by labelling of specific regions/tissues and tracking their deformation, we observed that the unsegmented region does not generate additional tissue volume at the caudal tip. Instead, it contributes to axis elongation by extensive tissue deformation at constant volume. We show that volumetric growth occurs in the segmented portion of the axis and can be attributed to an increase in the size and length of the spinal cord and notochord. FGF inhibition blocks tissue convergence within the tailbud and unsegmented region rather than affecting volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis, even if by different cell behaviours. Finally, a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse reveal a differential contribution of volumetric growth that is linked to a switch between external and internal modes of development. We propose that posterior growth is not a conserved mechanism to drive axis elongation in vertebrates. It is instead associated with an overall increase in growth characteristic of internally developing embryos that undergo embryonic development concomitantly with an increase in energy supply from the female parent.


2015 ◽  
Vol 309 (7) ◽  
pp. C457-C469 ◽  
Author(s):  
Ayushi Vashisht ◽  
Mohamed Trebak ◽  
Rajender K. Motiani

Calcium (Ca2+) regulates a plethora of cellular functions including hallmarks of cancer development such as cell cycle progression and cellular migration. Receptor-regulated calcium rise in nonexcitable cells occurs through store-dependent as well as store-independent Ca2+ entry pathways. Stromal interaction molecules (STIM) and Orai proteins have been identified as critical constituents of both these Ca2+ influx pathways. STIMs and Orais have emerged as targets for cancer therapeutics as their altered expression and function have been shown to contribute to tumorigenesis. Recent data demonstrate that they play a vital role in development and metastasis of a variety of tumor types including breast, prostate, cervical, colorectal, brain, and skin tumors. In this review, we will retrospect the data supporting a key role for STIM1, STIM2, Orai1, and Orai3 proteins in tumorigenesis and discuss the potential of targeting these proteins for cancer therapy.


Development ◽  
1979 ◽  
Vol 51 (1) ◽  
pp. 27-50
Author(s):  
Murray Pearson ◽  
Tom Elsdale

Somitogenesis is described in two species of anuran amphibians, Xenopus laevis and Rana temporaria, in which the cellular mechanics of somite formation are distinctly different. Heat shocks are employed to demonstrate a wave of cellular change which precedes somite formation down the body axis. This prior wave is shown to be kinematic. It is not a propagated wave. It is a consequence of the temporal activities of the cells laid out in space, but there is no evidence that these activities depend upon an interpretation of their position. Heat shocks cause characteristic segmental abnormalities over a zone of somites which is formed several hours after the shock. Evidence from double heat shock experiments suggests that the pattern of abnormality is the result of (i) a disturbance of co-ordination between pre-somitic cells, and (ii) the time available to those cells for recovery before they are recruited into a segmental pre-pattern at the time of passage of the prior wave. It is a temporal coordination that is disturbed and subsequently recovered following a heat shock. This temporal co-ordination of pre-somitic cells does not depend upon position along the axis. The evidence for two physiologically independent temporal patterns of cellular processes, which interact to specify the segmental pattern of somites (their size, shape and number), gives experimental support for the theoretical account of somitogenesis proposed by Cooke & Zeeman (1976).


Author(s):  
Nazli Alizadeh-Tabrizi ◽  
Stefan Hall ◽  
Christian Lehmann

Intravital microscopy (IVM) is a unique imaging method providing insights in cellular functions and interactions in real-time, without the need for tissue extraction from the body. IVM of the lungs has specific challenges such as restricted organ accessibility, respiratory movements, and limited penetration depth. Various surgical approaches and microscopic setups have been adapted in order to overcome these challenges. Among others, these include the development of suction stabilized lung windows and the use of more advanced optical techniques. Consequently, lung IVM has uncovered mechanisms of leukocyte recruitment and function in several models of pulmonary inflammation and infection. This review focuses on bacterial pneumonia, aspiration pneumonia, sepsis-induced acute lung Injury, and cystic fibrosis, as examples of lung inflammation and infection. In addition, critical details of intravital imaging techniques of the lungs are discussed.


Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Beric R. Henderson

Inherited mutations in theBRCA1gene predispose to a higher risk of breast/ovarian cancer. The BRCA1 tumor suppressor is a 1863 amino acid protein with multiple protein interaction domains that facilitate its roles in regulating DNA repair and maintenance, cell cycle progression, transcription, and cell survival/apoptosis. BRCA1 was first identified as a nuclear phosphoprotein, but has since been shown to contain different transport sequences including nuclear export and nuclear localization signals that enable it to shuttle between specific sites within the nucleus and cytoplasm, including DNA repair foci, centrosomes, and mitochondria. BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways. This paper will focus on the transport, dynamics, and multiple intracellular destinations of BRCA1 with emphasis on how regulation of these events has impact on, and determines, a broad range of important cellular functions.


2020 ◽  
Vol 27 (3) ◽  
pp. 201-209
Author(s):  
Syed Saqib Ali ◽  
Mohammad Khalid Zia ◽  
Tooba Siddiqui ◽  
Haseeb Ahsan ◽  
Fahim Halim Khan

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood. Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.


Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 89-91
Author(s):  
Shin-ichi Tate

The field of molecular biology has provided great insights into the structure and function of key molecules. Thanks to this area of research, we can now grasp the biological details of DNA and have characterised an enormous number of molecules in massive data bases. These 'biological periodic tables' have allowed scientists to connect molecules to particular cellular events, furthering scientific understanding of biological processes. However, molecular biology has yet to answer questions regarding 'higher-order' molecular architecture, such as that of chromatin. Chromatin is the molecular material that serves as the building block for chromosomes, the structures that carry an organism's genetic information inside of the cell's nucleus. Understanding the physical properties of chromatin is crucial in developing a more thorough picture of how chromatin's structure relate to its key cellular functions. Moreover, by establishing a physical model of chromatin, scientists will be able to open the doors into the true inner workings of the cell nucleus. Professor Shin-ichi Tate and his team of researchers at Hiroshima University's Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), are attempting to do just that. Through a five-year grant funded by the Platform for Dynamic Approaches to Living Systems from the Ministry of Education, Culture, Sports, Science and Technology, Tate is aiming to gain a clearer understanding of the structure and dynamics of chromatin.


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