scholarly journals Visceral organ morphogenesis via calcium-patterned muscle contractions

2021 ◽  
Author(s):  
Noah Prentice Mitchell ◽  
Dillon Cislo ◽  
Suraj Shankar ◽  
yuzheng Lin ◽  
Boris I Shraiman ◽  
...  
Keyword(s):  
Time Course ◽  
Hox Genes ◽  
Shape Change ◽  
Muscle Layer ◽  
Convergent Extension ◽  
Visceral Organ ◽  
Adjacent Layer ◽  
Light Sheet Microscopy ◽  
Shape Changes

How organs achieve their final shape is a problem at the interface between physics and developmental biology. Organs often involve multiple interacting tissue layers that must be coordinated to orchestrate the complex shape changes of development. Intense study has uncovered genetic and physical ingredients driving the form of monolayer tissue. Yet, tracing dynamics across tissue layers and across scales -- from cell to tissue, to entire organs -- remains an outstanding challenge. Here, we study the midgut of Drosophila embryos as a model visceral organ to reconstruct in toto the dynamics of multi-layer organ formation in vivo. Using light-sheet microscopy, genetics, computer vision, and tissue cartography, we extract individual tissue layers to map the time course of shape across scales. We identify the kinematic mechanism driving the shape change due to tissue layer interactions by linking out-of-plane motion to active contraction patterns, revealing a convergent extension process in which cells deform as they flow into deepening folds. Acute perturbations of contractility in the muscle layer using non-neuronal optogenetics reveals that these contraction patterns are due to muscle activity, which induces cell shape changes in the adjacent endoderm layer. This induction cascade relies on high frequency calcium pulses in the muscle layer, under the control of hox genes. Inhibition of targets of calcium involved in myosin phosphorylation abolishes constrictions. Our study of multi-layer organogenesis reveals how genetic patterning in one layer triggers a dynamic molecular mechanism to control a physical process in the adjacent layer, orchestrating whole-organ shape change.

Platelet Shape Change Evoked by Selective Activation of P2X1 Purinoceptors with α,β-Methylene ATP

2001 ◽  
Vol 85 (02) ◽  
pp. 303-308 ◽  
Author(s):  
Michael Rolf ◽  
Charles Brearley ◽  
Martyn Mahaut-Smith
Keyword(s):  
Inhibitory Action ◽  
Light Transmission ◽  
Shape Change ◽  
Second Messengers ◽  
Receptor Activation ◽  
Selective Activation ◽  
The Relationship ◽  
Shape Changes ◽  
Platelet Shape

SummarySimultaneous measurements of [Ca2+]i and light transmission were used to examine the relationship between P2X1 receptor activation and functional platelet responses. The P2X1 agonist α,β-MeATP evoked a transient [Ca2+]i increase and a reversible decrease in light transmission; both responses required external Ca2+ and the nucleotidase apyrase. The transmission response was due to shape change only, verified by scanning electron microscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. α,β-MeATP stimulated smaller shape changes than ADP, however P2X1 responses had a lifespan of <2 h following resuspension in saline and may be considerably larger in vivo. A peak [Ca2+]i increase of >50 nM was required for detectable shape change. Overlap of concentration-response relationships for α,β-MeATP-evoked [Ca2+]i and shape change suggests that other second messengers are not involved. Therefore, the physiological P2X1 agonist ATP can contribute to platelet activation, in contrast to its previously described inhibitory action at metabotropic platelet purinoceptors.

scholarly journals Autonomous epithelial folding induced by an intracellular mechano–polarity feedback loop

2021 ◽  
Author(s):  
Fu-Lai Wen ◽  
Chun Wai Kwan ◽  
Yu-Chiun Wang ◽  
Tatsuo Shibata
Keyword(s):  
Feedback Loop ◽  
Shape Change ◽  
Reaction Diffusion ◽  
Emergent Properties ◽  
Cell Geometry ◽  
Biochemical Mechanisms ◽  
Fold Formation ◽  
Folded Structures ◽  
Shape Changes

AbstractEpithelial tissues form folded structures during embryonic development and organogenesis. Whereas substantial efforts have been devoted to identifying mechanical and biochemical mechanisms that induce folding, how they interact remains poorly understood. Here we propose a mechano–biochemical model for dorsal fold formation in the early Drosophila embryo, an epithelial folding event induced by shifts of cell polarity. Based on experimentally observed apical domain homeostasis, we couple cell mechanics to polarity and find that mechanical changes following the initial polarity shifts alter cell geometry, which in turn influences the reaction-diffusion of polarity proteins, thus forming a feedback loop between mechanics and polarity. This model can induce spontaneous fold formation in silico, recapitulate polarity and shape changes observed in vivo, and confer robustness to tissue shape change against small fluctuations in mechanics and polarity. These findings reveal emergent properties of a developing epithelium under control of intracellular mechano–polarity coupling.

Effects of leukotrienes on isolated rat glomeruli and cultured mesangial cells

1986 ◽  
Vol 250 (5) ◽  
pp. F838-F844
Author(s):  
R. Barnett ◽  
P. Goldwasser ◽  
L. A. Scharschmidt ◽  
D. Schlondorff
Keyword(s):  
Surface Area ◽  
Mesangial Cells ◽  
Shape Change ◽  
Ang Ii ◽  
Planar Surface ◽  
Glomerular Function ◽  
Shape Changes ◽  
Isolated Rat

Several vasoactive substances influence glomerular function in vivo and alter glomerular surface area and prostaglandin (PG) synthesis in vitro. Leukotrienes (LT) LTC4 and LTD4 may also influence glomerular function in vivo and in the isolated perfused kidney. We therefore compared the effects of LT with those of angiotensin II (ANG II), arginine vasopressin (AVP), and platelet activating factor (PAF) on planar surface area of isolated rat glomeruli and the shape change of cultured mesangial cells and their PG synthesis. ANG II, AVP, and PAF decreased the surface area of isolated rat glomeruli by 10-14% with comparable changes induced by LTC4 and LTD4. Half-maximal effects of LTs were observed at approximately 10(-7) M. Incubation of cultured rat mesangial cells with LTC4 or LTD4 at 10(-7) and 10(-8) M was also associated with shape changes of the cells resulting in significant reductions in planar surface area in a dose- and time-dependent fashion similar to that noted previously with other vasoactive agents. In cells grown on a flexible silicone rubber support, LTD4 resulted in rapid increases in wrinkling of the mobile surface indicating that the shape change may represent cell contraction. The LT-mediated decrease in surface area of glomeruli and mesangial cells was partially antagonized by the LT inhibitor FPL-55712. In contrast to the 11- and 7-fold enhancement of PGE2 synthesis in cultured mesangial cells by ANG II or PAF, neither LTC4 nor LTD4 affected PGE2 production. These results demonstrate that LTC4 and LTD4 cause mesangial shape changes that in the whole glomerulus may decrease glomerular surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Shifting gears: dynamic muscle shape changes and force-velocity behavior in the medial gastrocnemius

2017 ◽  
Vol 123 (6) ◽  
pp. 1433-1442 ◽  
Author(s):  
Taylor J. M. Dick ◽  
James M. Wakeling
Keyword(s):  
Skeletal Muscle ◽  
Muscle Activation ◽  
Mechanical Performance ◽  
Shape Change ◽  
Muscle Thickness ◽  
Pennation Angle ◽  
Medial Gastrocnemius ◽  
Force Velocity ◽  
Shape Changes

When muscles contract, they bulge in thickness or in width to maintain a (nearly) constant volume. These dynamic shape changes are tightly linked to the internal constraints placed on individual muscle fibers and play a key functional role in modulating the mechanical performance of skeletal muscle by increasing its range of operating velocities. Yet to date we have a limited understanding of the nature and functional implications of in vivo dynamic muscle shape change under submaximal conditions. This study determined how the in vivo changes in medial gastrocnemius (MG) fascicle velocity, pennation angle, muscle thickness, and subsequent muscle gearing varied as a function of force and velocity. To do this, we obtained recordings of MG tendon length, fascicle length, pennation angle, and thickness using B-mode ultrasound and muscle activation using surface electromyography during cycling at a range of cadences and loads. We found that that increases in contractile force were accompanied by reduced bulging in muscle thickness, reduced increases in pennation angle, and faster fascicle shortening. Although the force and velocity of a muscle contraction are inversely related due to the force-velocity effect, this study has shown how dynamic muscle shape changes are influenced by force and not influenced by velocity.NEW & NOTEWORTHY During movement, skeletal muscles contract and bulge in thickness or width. These shape changes play a key role in modulating the performance of skeletal muscle by increasing its range of operating velocities. Yet to date the underlying mechanisms associated with muscle shape change remain largely unexplored. This study identified muscle force, and not velocity, as the mechanistic driving factor to allow for muscle gearing to vary depending on the contractile conditions during human cycling.

scholarly journals Geometric models to explore mechanisms of dynamic shape change in skeletal muscle

2018 ◽  
Vol 5 (5) ◽  
pp. 172371 ◽  
Author(s):  
Taylor J. M. Dick ◽  
James M. Wakeling
Keyword(s):  
Skeletal Muscle ◽  
Shape Change ◽  
Geometric Constraints ◽  
Muscle Performance ◽  
Medial Gastrocnemius ◽  
Type Model ◽  
Length Changes ◽  
Shape Changes ◽  
Dynamic Shape

Skeletal muscle bulges when it contracts. These three-dimensional (3D) dynamic shape changes play an important role in muscle performance by altering the range of fascicle velocities over which a muscle operates. However traditional muscle models are one-dimensional (1D) and cannot fully explain in vivo shape changes. In this study we compared medial gastrocnemius behaviour during human cycling (fascicle length changes and rotations) predicted by a traditional 1D Hill-type model and by models that incorporate two-dimensional (2D) and 3D geometric constraints to in vivo measurements from B-mode ultrasound during a range of mechanical conditions ranging from 14 to 44 N m and 80 to 140 r.p.m. We found that a 1D model predicted fascicle lengths and pennation angles similar to a 2D model that allowed the aponeurosis to stretch, and to a 3D model that allowed for aponeurosis stretch and variable shape changes to occur. This suggests that if the intent of a model is to predict fascicle behaviour alone, then the traditional 1D Hill-type model may be sufficient. Yet, we also caution that 1D models are limited in their ability to infer the mechanisms by which shape changes influence muscle mechanics. To elucidate the mechanisms governing muscle shape change, future efforts should aim to develop imaging techniques able to characterize whole muscle 3D geometry in vivo during active contractions.

scholarly journals Autonomous epithelial folding induced by an intracellular mechano–polarity feedback loop

2021 ◽  
Vol 17 (12) ◽  
pp. e1009614
Author(s):  
Fu-Lai Wen ◽  
Chun Wai Kwan ◽  
Yu-Chiun Wang ◽  
Tatsuo Shibata
Keyword(s):  
Cell Mechanics ◽  
Feedback Loop ◽  
Shape Change ◽  
Reaction Diffusion ◽  
Emergent Properties ◽  
Biochemical Mechanisms ◽  
Fold Formation ◽  
Folded Structures ◽  
Shape Changes

Epithelial tissues form folded structures during embryonic development and organogenesis. Whereas substantial efforts have been devoted to identifying mechanical and biochemical mechanisms that induce folding, whether and how their interplay synergistically shapes epithelial folds remains poorly understood. Here we propose a mechano–biochemical model for dorsal fold formation in the early Drosophila embryo, an epithelial folding event induced by shifts of cell polarity. Based on experimentally observed apical domain homeostasis, we couple cell mechanics to polarity and find that mechanical changes following the initial polarity shifts alter cell geometry, which in turn influences the reaction-diffusion of polarity proteins, thus forming a feedback loop between cell mechanics and polarity. This model can induce spontaneous fold formation in silico, recapitulate polarity and shape changes observed in vivo, and confer robustness to tissue shape change against small fluctuations in mechanics and polarity. These findings reveal emergent properties of a developing epithelium under control of intracellular mechano–polarity coupling.

scholarly journals Ex vivolive cell tracking in kidney organoids using light sheet fluorescence microscopy

2017 ◽  
Author(s):  
Marie Held ◽  
Ilaria Santeramo ◽  
Bettina Wilm ◽  
Patricia Murray ◽  
Raphaël Lévy
Keyword(s):  
Fluorescence Microscopy ◽  
Time Course ◽  
Cell Tracking ◽  
Organic Anion ◽  
Light Sheet ◽  
Differentiation Potential ◽  
Light Sheet Microscopy ◽  
Kidney Organoids

AbstractScreening cells for their differentiation potential requires a combination of tissue culture models and imaging methods that allow for long-term tracking of the location and function of cells. Embryonic kidney re-aggregationin vitroassays have been established which allow for the monitoring of organotypic cell behaviour in re-aggregated and chimeric renal organoids. However, evaluation of cell integration is hampered by the high photonic load of standard fluorescence microscopy which poses challenges for imaging three-dimensional systems in real-time over a time course. Therefore, we employed light sheet microscopy, a technique that vastly reduces photobleaching and phototoxic effects. We have also developed a new method for culturing the re-aggregates which involves immersed culture, generating organoids which more closely reflect developmentin vivo. To facilitate imaging from various angles, we embedded the organoids in a freely rotatable hydrogel cylinder. Endpoint fixing and staining were performed to provide additional biomolecular information. We succeeded in imaging labelled cells within re-aggregated kidney organoids over 15 hours and tracking their fate while simultaneously monitoring the development of organotypic morphological structures. Our results show that Wt1-expressing embryonic kidney cells obtained from transgenic mice could integrate into re-aggregated chimeric kidney organoids and contribute to developing nephrons. Furthermore, the nascent proximal tubules that formed in the re-aggregated tissues using the new culture method displayed secretory function, as evidenced by their ability to secrete an organic anion mimic into the tubular lumen.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

1986 ◽  
Vol 56 (02) ◽  
pp. 147-150 ◽  
Author(s):  
V Pengo ◽  
M Boschello ◽  
A Marzari ◽  
M Baca ◽  
L Schivazappa ◽  
...  
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Ex Vivo ◽  
Early Stage ◽  
Shape Change ◽  
Adenosine Diphosphate ◽  
Dose Dependent ◽  
Plateletderived Growth Factor ◽  
Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

Time Course Change of the Heat-generating Capability of Dextran Magnetite Complex (DM) in vivo.

2001 ◽  
Vol 17 (2) ◽  
pp. 85-91 ◽  
Author(s):  
MICHIHIDE MITSUMORI ◽  
TORU SHIBATA ◽  
YASUSHI NAGATA ◽  
MASAHIRO HIRAOKA ◽  
MASAKATSU HASEGAWA ◽  
...  
Keyword(s):  
Time Course
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