Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

Physiology ◽  
2012 ◽  
Vol 27 (3) ◽  
pp. 148-155 ◽  
Author(s):  
Nikè V. J. A. Büller ◽  
Sanne L. Rosekrans ◽  
Jessica Westerlund ◽  
Gijs R. van den Brink
Keyword(s):  
Cell Proliferation ◽  
Negative Feedback ◽  
Intestinal Epithelium ◽  
Hedgehog Signaling ◽  
Dynamic Equilibrium ◽  
Indian Hedgehog ◽  
Feedback Signal ◽  
Epithelial Integrity

Homeostasis of the rapidly renewing intestinal epithelium depends on a balance between cell proliferation and loss. Indian hedgehog (Ihh) acts as a negative feedback signal in this dynamic equilibrium. We discuss recent evidence that Ihh may be one of the key epithelial signals that indicates epithelial integrity to the underlying mesenchyme.

scholarly journals Synovial Joint Formation during Mouse Limb Skeletogenesis: Roles of Indian Hedgehog Signaling

2007 ◽  
Vol 1116 (1) ◽  
pp. 100-112 ◽  
Author(s):  
E. KOYAMA ◽  
T. OCHIAI ◽  
R. B. ROUNTREE ◽  
D. M. KINGSLEY ◽  
M. ENOMOTO-IWAMOTO ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Indian Hedgehog ◽  
Synovial Joint ◽  
Joint Formation ◽  
Mouse Limb

A noble extended stochastic logistic model for cell proliferation with density-dependent parameters

2021 ◽  
Author(s):  
Trina Roy ◽  
Sinchan Ghosh ◽  
Bapi Saha ◽  
Sabyasachi Bhattacharya
Keyword(s):  
Cell Proliferation ◽  
Cell Density ◽  
Negative Feedback ◽  
Deterministic Model ◽  
Culture Media ◽  
Logistic Growth ◽  
Density Dependent ◽  
Proposed Model ◽  
Dependent Cell ◽  
Growth Inhibiting

Abstract Cell proliferation often experiences a density-dependent intrinsic proliferation rate (IPR) and negative feedback from growth-inhibiting molecules in culture media. The lack of flexible models with explanatory parameters fails to capture such a proliferation mechanism. We propose an extended logistic growth law with the density-dependent IPR and additional negative feedback. The extended parameters of the proposed model can be interpreted as density-dependent cell-cell cooperation and negative feedback on cell proliferation. Moreover, we incorporate further density regulation for flexibility in the model through environmental resistance on cells. The proposed growth law has similarities with the strong Allee model and harvesting phenomenon. We also develop the stochastic analog of the deterministic model by representing possible heterogeneity in growth-inhibiting molecules and environmental perturbation of the culture setup as correlated multiplicative and additive noises. The model provides a maximum sustainable stable cell density (MSSCD) and a new fitness measure for proliferative cells. The proposed model shows superiority to the logistic law after fitting to real cell culture datasets. We illustrate both MSSCD and the new cell fitness for a range of parameters. The cell density distributions reveal the chance of overproliferation, underproliferation, or decay for different parameter sets under the deterministic and stochastic setups.

Integrated control of cell proliferation and cell death by the c- myc oncogene

1994 ◽  
Vol 345 (1313) ◽  
pp. 269-275 ◽  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Transcriptional Activation ◽  
Dynamic Equilibrium ◽  
Growth Arrest ◽  
Deletion Mapping ◽  
Potent Inducer ◽  
Cellular Environment ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

Regulation of multicellular architecture involves a dynamic equilibrium between cell proliferation, differentiation with consequent growth arrest, and cell death. Apoptosis is one particular form of active cell death that is extremely rapid and characterized by auto-destruction of chromatin, cellular blebbing and condensation, and vesicularization of internal components. The c- myc proto-oncogene encodes an essential component of the cell’s proliferative machinery and its deregulated expression is implicated in most neoplasms. Intriguingly, c- myc can also act as a potent inducer of apoptosis. Myc-induced apoptosis occurs only in cells deprived of growth factors or forcibly arrested with cytostatic drugs. Myc-induced apoptosis is dependent upon the level at which it is expressed and deletion mapping shows that regions of c-Myc required for apoptosis overlap with regions necessary for co-transformation, autoregulation, inhibition of differentiation, transcriptional activation and sequence-specific DNA binding. Moreover, induction of apoptosis by c-Myc requires association with c-Myc’s heterologous partner, Max. All of this strongly implies that c-Myc drives apoptosis through a transcriptional mechanism: presumably by modulation of target genes. Two simple models can be invoked to explain the induction of apoptosis by c-Myc. One holds that death arises from a conflict in growth signals which is generated by the inappropriate or unscheduled expression of c-Myc under conditions that would normally promote growth arrest. In this ‘Conflict’ model, induction of apoptosis is not a normal function of c-Myc but a pathological manifestation of its deregulation. It thus has significance only for models of carcinogenic progression in which myc genes are invariably disrupted. The other model holds that induction of apoptosis is a normal obligate function of c-Myc which is modulated by specific survival factors. Thus, every cell that enters the cycle invokes an obligate abort suicide pathway which must be continuously suppressed by signals from the immediate cellular environment for the proliferating cell to survive. Evidence will be presented supporting this second ‘Dual Signal’ model for cell growth and survival, and its widespread implications will be discussed.

scholarly journals Negative feedback in ants: crowding results in less trail pheromone deposition

2013 ◽  
Vol 10 (81) ◽  
pp. 20121009 ◽  
Author(s):  
Tomer J. Czaczkes ◽  
Christoph Grüter ◽  
Francis L. W. Ratnieks
Keyword(s):  
Negative Feedback ◽  
Trail Pheromone ◽  
Distribution Networks ◽  
Feedback Mechanism ◽  
Lasius Niger ◽  
Feedback Signal ◽  
Control Mechanisms ◽  
Negative Feedback Mechanism ◽  
Self Organized ◽  
Fold Reduction

Crowding in human transport networks reduces efficiency. Efficiency can be increased by appropriate control mechanisms, which are often imposed externally. Ant colonies also have distribution networks to feeding sites outside the nest and can experience crowding. However, ants do not have external controllers or leaders. Here, we report a self-organized negative feedback mechanism, based on local information, which downregulates the production of recruitment signals in crowded parts of a network by Lasius niger ants. We controlled crowding by manipulating trail width and the number of ants on a trail, and observed a 5.6-fold reduction in the number of ants depositing trail pheromone from least to most crowded conditions. We also simulated crowding by placing glass beads covered in nest-mate cuticular hydrocarbons on the trail. After 10 bead encounters over 20 cm, forager ants were 45 per cent less likely to deposit pheromone. The mechanism of negative feedback reported here is unusual in that it acts by downregulating the production of a positive feedback signal, rather than by direct inhibition or the production of an inhibitory signal.

scholarly journals Novel chicken two-dimensional intestinal model comprising all key epithelial cell types and a mesenchymal sub-layer

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Brigid Orr ◽  
Kate Sutton ◽  
Sonja Christian ◽  
Tessa Nash ◽  
Helle Niemann ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Cell Biology ◽  
Ex Vivo ◽  
Innate Immune ◽  
Intestinal Cell ◽  
Two Dimensional ◽  
Immune Functions ◽  
Ex Vivo Model ◽  
Isolated Cells ◽  
Epithelial Integrity

AbstractThe intestinal epithelium plays a variety of roles including providing an effective physical barrier and innate immune protection against infection. Two-dimensional models of the intestinal epithelium, 2D enteroids, are a valuable resource to investigate intestinal cell biology and innate immune functions and are suitable for high throughput studies of paracellular transport and epithelial integrity. We have developed a chicken 2D enteroid model that recapitulates all major differentiated cell lineages, including enterocytes, Paneth cells, Goblet cells, enteroendocrine cells and leukocytes, and self-organises into an epithelial and mesenchymal sub-layer. Functional studies demonstrated the 2D enteroids formed a tight cell layer with minimal paracellular flux and a robust epithelial integrity, which was maintained or rescued following damage. The 2D enteroids were also able to demonstrate appropriate innate immune responses following exposure to bacterial endotoxins, from Salmonella enterica serotype Typhimurium and Bacillus subtilis. Frozen 2D enteroids cells when thawed were comparable to freshly isolated cells. The chicken 2D enteroids provide a useful ex vivo model to study intestinal cell biology and innate immune function, and have potential uses in screening of nutritional supplements, pharmaceuticals, and bioactive compounds.

Hedgehog signals regulate multiple aspects of gastrointestinal development

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2763-2772 ◽  
Author(s):  
M. Ramalho-Santos ◽  
D.A. Melton ◽  
A.P. McMahon
Keyword(s):  
Gastrointestinal Tract ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Critical Role ◽  
Indian Hedgehog ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mesodermal Origin ◽  
Gut Endoderm

The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells of mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis of the gut and its derivatives. We have assessed the function of Sonic hedgehog and Indian hedgehog genes, which encode members of the Hedgehog family of cell signals. Both are expressed in gut endoderm, whereas target genes are expressed in discrete layers in the mesenchyme. It was unclear whether functional redundancy between the two genes would preclude a genetic analysis of the roles of Hedgehog signaling in the mouse gut. We show here that the mouse gut has both common and separate requirements for Sonic hedgehog and Indian hedgehog. Both Sonic hedgehog and Indian hedgehog mutant mice show reduced smooth muscle, gut malrotation and annular pancreas. Sonic hedgehog mutants display intestinal transformation of the stomach, duodenal stenosis (obstruction), abnormal innervation of the gut and imperforate anus. Indian hedgehog mutants show reduced epithelial stem cell proliferation and differentiation, together with features typical of Hirschsprung's disease (aganglionic colon). These results show that Hedgehog signals are essential for organogenesis of the mammalian gastrointestinal tract and suggest that mutations in members of this signaling pathway may be involved in human gastrointestinal malformations.

The Role of Indian Hedgehog Signaling in Tendon Response to Subacromial Impingement: Evaluation Using a Mouse Model

2021 ◽  
pp. 036354652110622
Author(s):  
Yulei Liu ◽  
Xiang-Hua Deng ◽  
Xueying Zhang ◽  
Ting Cong ◽  
Daoyun Chen ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Biomechanical Testing ◽  
Indian Hedgehog ◽  
Control Group ◽  
Subacromial Impingement ◽  
Subacromial Space ◽  
Gradual Improvement

Background: The underlying cellular and molecular mechanisms involved in the development of tendinopathy due to subacromial supraspinatus tendon (SST) impingement and the response to subsequent removal of impingement remain unknown. Purpose: To investigate the involvement of Indian hedgehog (IHH) signaling in the development of SST tendinopathy and the subsequent healing process after the relief of subacromial impingement in a novel mouse shoulder impingement model. Study Design: Controlled laboratory study. Methods: A total of 48 male wild-type C57BL/6 mice were used in this study. Supraspinatus tendinopathy was induced by inserting a microsurgical clip into the subacromial space bilaterally. Eleven mice were sacrificed at 4 weeks after surgery to establish impingement baseline; 24 mice underwent clip removal at 4 weeks after surgery and then were euthanized at 2 or 4 weeks after clip removal. Thirteen mice without surgical intervention were utilized as the control group. All SSTs were evaluated with biomechanical testing; quantitative histomorphometry after staining with hematoxylin and eosin, Alcian blue, and picrosirius red; and immunohistochemical staining (factor VIII, IHH, Patched1 [PTCH1], and glioma-associated oncogene homolog 1 [GLI1]). Results: The mean failure force and stiffness in the 4-week impingement group decreased significantly compared with the control group ( P < .001) and gradually increased at 2 and 4 weeks after clip removal. Histological analysis demonstrated increased cellularity and disorganized collagen fibers in the SST, with higher modified Bonar scores at 4 weeks, followed by gradual improvement after clip removal. The IHH-positive area and PTCH1- and GLI1-positive cell percentages significantly increased after 4 weeks of clip impingement (20.64% vs 2.06%, P < .001; 53.9% vs 28.03%, P = .016; and 30% vs 12.19%, P = .036, respectively) and continuously increased after clip removal. Conclusion: The authors’ findings suggest that the hedgehog signaling pathway and its downstream signaling mediator and target GLI1 may play a role in the development and healing process of rotator cuff tendinopathy due to extrinsic rotator cuff impingement. Clinical Relevance: This study suggests the potential for the hedgehog pathway, together with its downstream targets, as candidates for further study as potential therapeutic targets in the treatment of supraspinatus tendinopathy.

Indian Hedgehog Signaling in Osteoarthritis

2020 ◽  
pp. 652-657
Author(s):  
Shaowei Wang ◽  
Mengbo Zhu ◽  
Xiaochun Wei ◽  
Lei Wei
Keyword(s):  
Hedgehog Signaling ◽  
Indian Hedgehog
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