scholarly journals Mechanical Coupling Coordinates the Co-elongation of Axial and Paraxial Tissues in Avian Embryos

2018 ◽  
Author(s):  
Fengzhu Xiong ◽  
Wenzhe Ma ◽  
Bertrand Bénazéraf ◽  
L. Mahadevan ◽  
Olivier Pourquié
Keyword(s):  
Cell Motility ◽  
Feedback Loop ◽  
Tissue Growth ◽  
Positive Feedback Loop ◽  
General Role ◽  
Avian Embryos ◽  
Mechanical Coupling ◽  
A Cell ◽  
Cell Intercalation

SUMMARYTissues undergoing morphogenesis impose mechanical effects on one another. How developmental programs adapt to or take advantage of these effects remains poorly explored. Here, using a combination of live imaging, modeling, and microsurgical perturbations, we show that the axial and paraxial tissues in the forming avian embryonic body coordinate their rates of elongation through mechanical interactions. First, a cell motility gradient drives paraxial presomitic mesoderm (PSM) expansion, resulting in compression of the axial neural tube and notochord; second, elongation of axial tissues driven by PSM compression and polarized cell intercalation pushes the caudal progenitor domain posteriorly; finally, the axial push drives progenitors to emigrate into the PSM to maintain tissue growth and cell motility. These interactions form an engine-like positive feedback loop, which ensures the tissue-coupling and self-sustaining characteristics of body elongation. Our results suggest a general role of inter-tissue forces in the coordination of complex morphogenesis involving distinct tissues.

scholarly journals Dual Role of Cell-Cell Adhesion In Tumor Suppression and Proliferation Due to Collective Mechanosensing

2019 ◽  
Author(s):  
Abdul N Malmi-Kakkada ◽  
Xin Li ◽  
Sumit Sinha ◽  
D. Thirumalai
Keyword(s):  
Cell Adhesion ◽  
Adhesion Strength ◽  
Feedback Loop ◽  
Local Stress ◽  
Feedback Mechanism ◽  
Tissue Growth ◽  
Inhibition Of Proliferation ◽  
A Cell ◽  
Cell Cell

AbstractIt is known that mechanical interactions couple a cell to its neighbors, enabling a feedback loop to regulate tissue growth. However, the interplay between cell-cell adhesion strength, local cell density and force fluctuations in regulating cell proliferation is poorly understood. Here, we show that spatial variations in the tumor growth rates, which depend on the location of cells within tissue spheroids, are strongly influenced by cell-cell adhesion. As the strength of the cell-cell adhesion increases, intercellular pressure initially decreases, enabling dormant cells to more readily enter into a proliferative state. We identify an optimal cell-cell adhesion regime where pressure on a cell is a minimum, allowing for maximum proliferation. We use a theoretical model to validate this novel collective feedback mechanism coupling adhesion strength, local stress fluctuations and proliferation. Our results predict the existence of a non-monotonic proliferation behavior as a function of adhesion strength, consistent with experimental results. Several experimental implications of the proposed role of cell-cell adhesion in proliferation are quantified, making our model predictions amenable to further experimental scrutiny. We show that the mechanism of contact inhibition of proliferation, based on a pressure-adhesion feedback loop, serves as a unifying mechanism to understand the role of cell-cell adhesion in proliferation.

scholarly journals Autocrine signaling by an Aplysia neurotrophin forms a presynaptic positive feedback loop

2018 ◽  
Vol 115 (47) ◽  
pp. E11168-E11177 ◽  
Author(s):  
Iksung Jin ◽  
Hiroshi Udo ◽  
Russell Nicholls ◽  
Huixiang Zhu ◽  
Eric R. Kandel ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
Autocrine Signaling ◽  
Positive Feedback Loop ◽  
Short Term Plasticity ◽  
Extracellular Signaling ◽  
Presynaptic Protein ◽  
Long Term Facilitation

Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.

scholarly journals Essential role of Bmp signaling and its positive feedback loop in the early cell fate evolution of chordates

2013 ◽  
Vol 382 (2) ◽  
pp. 538-554 ◽  
Author(s):  
Iryna Kozmikova ◽  
Simona Candiani ◽  
Peter Fabian ◽  
Daniela Gurska ◽  
Zbynek Kozmik
Keyword(s):  
Cell Fate ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Essential Role ◽  
Bmp Signaling ◽  
Positive Feedback Loop

scholarly journals Chp1-Tas3 Interaction Is Required To Recruit RITS to Fission Yeast Centromeres and for Maintenance of Centromeric Heterochromatin

2008 ◽  
Vol 28 (7) ◽  
pp. 2154-2166 ◽  
Author(s):  
Jennifer L. DeBeauchamp ◽  
Arian Moses ◽  
Victoria J. P. Noffsinger ◽  
Dagny L. Ulrich ◽  
Godwin Job ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Feedback Loop ◽  
Histone H3 ◽  
Adaptor Protein ◽  
Centromeric Heterochromatin ◽  
Chromosome Loss ◽  
Methyltransferase Activity ◽  
Interaction Domain ◽  
Positive Feedback Loop

ABSTRACT The maintenance of centromeric heterochromatin in fission yeast relies on the RNA interference-dependent complexes RITS (RNA-induced transcriptional silencing complex) and RDRC (RNA-directed RNA polymerase complex), which cooperate in a positive feedback loop to recruit high levels of histone H3 K9 methyltransferase activity to centromeres and to promote the assembly and maintenance of centromeric heterochromatin. However, it is unclear how these complexes are targeted to chromatin. RITS comprises Chp1, which binds K9-methylated histone H3; Ago1, which binds short interfering (siRNAs); the adaptor protein Tas3, which links Ago1 to Chp1; and centromeric siRNAs. We have generated mutants in RITS to determine the contribution of the two potential chromatin-targeting proteins Chp1 and Ago1 to the centromeric recruitment of RITS. Mutations in Tas3 that disrupt Ago1 binding are permissive for RITS recruitment and maintain centromeric heterochromatin, but the role of Tas3's interaction with Chp1 is unknown. Here, we define the Chp1 interaction domain of Tas3. A strain expressing a tas3 mutant that cannot bind Chp1 (Tas3Δ 10-24) failed to maintain centromeric heterochromatin, with a loss of centromeric siRNAs, a failure to recruit RITS and RDRC to centromeres, and high levels of chromosome loss. These findings suggest a pivotal role for Chp1 and its association with Tas3 for the recruitment of RITS, RDRC, and histone H3 K9 methyltransferase activity to centromeres.

scholarly journals Clustering-based positive feedback between a kinase and its substrate enables effective T-cell receptor signaling

2020 ◽  
Author(s):  
Elliot Dine ◽  
Ellen H. Reed ◽  
Jared E. Toettcher
Keyword(s):  
T Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Src Family Kinases ◽  
Molecular Organization ◽  
List Type ◽  
Positive Feedback Loop ◽  
Downstream Signaling ◽  
Protein Clusters

AbstractProtein clusters and condensates are pervasive in mammalian signaling. Yet how the signaling capacity of higher-order assemblies differs from simpler forms of molecular organization is still poorly understood. Here, we present an optogenetic approach to switch between light-induced clusters and simple protein heterodimers with a single point mutation. We apply this system to study how clustering affects signaling from the kinase Zap70 and its substrate LAT, proteins that normally form membrane-localized clusters during T cell activation. We find that light-induced clusters of LAT and Zap70 trigger potent activation of downstream signaling pathways even in non-T cells, whereas one-to-one dimers do not. We provide evidence that clusters harbor a local positive feedback loop between three components: Zap70, LAT, and Src-family kinases that bind to phosphorylated LAT and further activate Zap70. Overall, our study provides evidence for a specific role of protein condensates in cell signaling, and identifies a simple biochemical circuit that can robustly sense protein oligomerization state.Highlights-A general system for studying the role of protein clusters versus dimers.-Membrane clusters of the kinase Zap70 and its substrate LAT trigger potent downstream signaling.-Clustering Zap70 with LAT is required for full activation of Zap70 kinase activity.-A positive feedback loop connects phosphorylated LAT to Zap70 activation via Src-family kinases.

scholarly journals Qian Yang Yu Yin Granule Improves Renal Injury of Hypertension by Regulating Metabolic Reprogramming Mediated by HIF-1α/PKM2 Positive Feedback Loop

2021 ◽  
Vol 12 ◽  
Author(s):  
Lichao Qian ◽  
Shuai Ren ◽  
Zhongchi Xu ◽  
Yawei Zheng ◽  
Lihua Wu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Metabolic Reprogramming ◽  
Hypertensive Nephropathy ◽  
Positive Feedback Loop ◽  
Tgf Β1

Protection against hypoxia injury is an important therapeutic strategy for treating hypertensive nephropathy. In this study, the effects of Qian Yang Yu Yin granule (QYYY) on spontaneously hypertensive rats fed with high salt diet and HEK293T cells exposed to hypoxia were investigated. After eight weeks’ treatment of QYYY, blood pressure, serum creatinine, serum cystatin C, blood urea nitrogen, urinary β2-microglobulin, urinary N-acetyl-β-glucosaminidase, and urinary microalbumin were assessed. The changes of hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2), glucose transport 1 (GLUT1), lactate dehydrogenase A (LDH-A), connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), ATP, lactate, pyruvate, and pathology were also assessed in vivo. HEK293T cells pre-treated with QYYY and/or HIF-1α over expressing cells were cultured in a three gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 h and then the expressions of HIF-1α, PKM2, GLUT1, LDH-A, CTGF, TGF-β1, ATP, lactate, and pyruvate were detected. Our results showed that QYYY promoted the indicators of renal inflammation and fibrosis mediated by HIF-1α/PKM2 positive feedback loop in vivo and vitro. Our findings indicated that QYYY treated hypertensive nephropathy by regulating metabolic reprogramming mediated by HIF-1α/PKM2 positive feedback loop.

scholarly journals Protective Role of Commensals against Clostridium difficile Infection via an IL-1β–Mediated Positive-Feedback Loop

2012 ◽  
Vol 189 (6) ◽  
pp. 3085-3091 ◽  
Author(s):  
Mizuho Hasegawa ◽  
Nobuhiko Kamada ◽  
Yizu Jiao ◽  
Meng Zhen Liu ◽  
Gabriel Núñez ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Protective Role ◽  
Positive Feedback Loop
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