An inductive role for the endoderm in Xenopus cardiogenesis

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 515-523 ◽  
Author(s):  
N. Nascone ◽  
M. Mercola
Keyword(s):  
Heart Tissue ◽  
Spemann Organizer ◽  
Multistep Process ◽  
Heart Formation ◽  
Organizer Activity ◽  
Presence And Absence ◽  
Necessary And Sufficient ◽  
Heart Induction

Heart induction in Xenopus has been thought to be dependent primarily on the interaction of the heart primordia with the Spemann organizer. We demonstrate, however, that signals derived from the deep dorsoanterior endoderm during early gastrulation are also essential for heart formation. The presence of deep endoderm dramatically enhances heart formation in explants of heart primordia, both in the presence and absence of organizer. Likewise, extirpation of the entire endoderm can decrease the frequency of heart formation in embryos that retain organizer activity. Finally, we show that the combined presence of both endoderm and organizer is necessary and sufficient to induce heart in ventral mesoderm explants that would not otherwise form heart tissue. Xenopus heart induction, therefore, may be a multistep process requiring separate dorsalization and cardiogenic signalling events. This is the first demonstration of a heart-inducing role for the endoderm in Xenopus, indicating that the mechanism of heart formation may be similar in most vertebrates.

scholarly journals Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype

2021 ◽  
Vol 13 (603) ◽  
pp. eabd1817
Author(s):  
Jacqueline M. Bliley ◽  
Mathilde C. S. C. Vermeer ◽  
Rebecca M. Duffy ◽  
Ivan Batalov ◽  
Duco Kramer ◽  
...  
Keyword(s):  
Dynamic Loading ◽  
Disease Modeling ◽  
Contractile Function ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Heart Tissue ◽  
Disease Phenotype ◽  
Heart Formation ◽  
Induced Pluripotent ◽  
And Function

The role that mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)–derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained contractile shortening of >10%. To do this, three-dimensional (3D) EHTs were integrated with an elastic polydimethylsiloxane strip providing mechanical preload and afterload in addition to enabling contractile force measurements based on strip bending. Our results demonstrated that dynamic loading improves the function of wild-type EHTs on the basis of the magnitude of the applied force, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output.

scholarly journals Dynamic Loading of Human Engineered Heart Tissue Enhances Contractile Function and Drives Desmosome-linked Disease Phenotype

2020 ◽  
Author(s):  
Jacqueline M. Bliley ◽  
Mathilde C.S.C Vermeer ◽  
Rebecca M. Duffy ◽  
Ivan Batalov ◽  
Duco Kramer ◽  
...  
Keyword(s):  
Dynamic Loading ◽  
Disease Modeling ◽  
Contractile Function ◽  
Induced Pluripotent Stem Cell ◽  
Heart Tissue ◽  
Disease Phenotype ◽  
Heart Formation ◽  
Induced Pluripotent ◽  
And Function ◽  
Engineered Heart Tissues

ABSTRACTThe role mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes in the heart. However, most EHT systems are unable to model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained fractional shortening of >10%. To do this, 3D EHTs are integrated with an elastic polydimethylsiloxane (PDMS) strip that provides mechanical pre- and afterload to the tissue in addition to enabling contractile force measurements based on strip bending. Our results demonstrate in wild-type EHTs that dynamic loading is beneficial based on the magnitude of the forces, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we use hiPSC–derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy (ACM) due to mutations in desmoplakin. We demonstrate that manifestation of this desmosome-linked disease state requires the dyn-EHT conditioning and that it cannot be induced using 2D or standard 3D EHT approaches. Thus, dynamic loading strategy is necessary to provoke a disease phenotype (diastolic lengthening, reduction of desmosome counts, and reduced contractility), which are akin to primary endpoints of clinical disease, such as chamber thinning and reduced cardiac output.Single Sentence SummaryDevelopment of a dynamic mechanical loading platform to improve contractile function of engineered heart tissues and study cardiac disease progression.

A role for Siamois in Spemann organizer formation

Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2581-2589 ◽  
Author(s):  
M.J. Fan ◽  
S.Y. Sokol
Keyword(s):  
Homeobox Gene ◽  
Early Embryo ◽  
Axis Formation ◽  
Beta Catenin ◽  
Wild Type ◽  
Spemann Organizer ◽  
Dna Binding Specificity ◽  
Organizer Activity ◽  
Special Region ◽  
Repression Domain

The vertebrate body plan is specified in the early embryo through the inductive influence of the organizer, a special region that forms on the dorsalmost side of the embryo at the beginning of gastrulation. In Xenopus, the homeobox gene Siamois is activated prior to gastrulation in the area of organizer activity and is capable of inducing a secondary body axis when ectopically expressed. To elucidate the function of endogeneous Siamois in dorsoventral axis formation, we made a dominant repressor construct (SE) in which the Siamois homeodomain was fused to an active repression domain of Drosophila engrailed. Overexpression of 1–5 pg of this chimeric mRNA in the early embryo blocks axis development and inhibits activation of dorsal, but not ventrolateral, marginal zone markers. At similar expression levels, SE proteins with altered DNA-binding specificity do not have the same effect. Coexpression of mRNA encoding wild-type Siamois, but not a mutated Siamois, restores dorsal development to SE embryos. Furthermore, SE strongly blocks axis formation triggered by beta-catenin but not by the organizer product noggin. These results suggest that Siamois function is essential for beta-catenin-mediated formation of the Spemann organizer, and that Siamois acts prior to noggin in specifying dorsal development.

scholarly journals Cleavage of Chordin by Xolloid Metalloprotease Suggests a Role for Proteolytic Processing in the Regulation of Spemann Organizer Activity

Cell ◽  
1997 ◽  
Vol 91 (3) ◽  
pp. 407-416 ◽  
Author(s):  
Stefano Piccolo ◽  
Eric Agius ◽  
Bin Lu ◽  
Shelley Goodman ◽  
Leslie Dale ◽  
...  
Keyword(s):  
Proteolytic Processing ◽  
Spemann Organizer ◽  
Organizer Activity

Spemann organizer activity of Smad10

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 137-146
Author(s):  
J.A. LeSueur ◽  
J.M. Graff
Keyword(s):  
Expression Profile ◽  
Functional Activity ◽  
Neural Tissue ◽  
Spemann Organizer ◽  
Isolation And Characterization ◽  
Dorsal Axis ◽  
Neural Tissues ◽  
Organizer Activity

The Spemann organizer induces neural tissue, dorsalizes mesoderm and generates a second dorsal axis. We report the isolation and characterization of Smad10, which has all three of these Spemann activities. Smad10 is expressed at the appropriate time to transduce Spemann signals endogenously. Like the organizer, Smad10 generates anterior and posterior neural tissues. Smad10 appears to function downstream of the Spemann organizer, consistent with a role in mediating organizer-derived signals. Interestingly, Smad10, unlike previously characterized mediators of Spemann activity, does not appear to block BMP signals. This finding, coupled with the functional activity and expression profile, suggests that Smad10 mediates Spemann action in a novel manner.

The extinction time of a general birth and death process with catastrophes

1986 ◽  
Vol 23 (04) ◽  
pp. 851-858 ◽  
Author(s):  
P. J. Brockwell
Keyword(s):  
Laplace Transform ◽  
Size Distribution ◽  
Sufficient Conditions ◽  
Necessary And Sufficient Conditions ◽  
Death Process ◽  
Extinction Time ◽  
Birth And Death Process ◽  
Different Types ◽  
The Laplace Transform ◽  
Necessary And Sufficient

The Laplace transform of the extinction time is determined for a general birth and death process with arbitrary catastrophe rate and catastrophe size distribution. It is assumed only that the birth rates satisfyλ0= 0,λj> 0 for eachj> 0, and. Necessary and sufficient conditions for certain extinction of the population are derived. The results are applied to the linear birth and death process (λj=jλ, µj=jμ) with catastrophes of several different types.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

Effects of Noise and Increased Vocal Intensity on Stuttering

1977 ◽  
Vol 20 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Sharon F. Garber ◽  
Richard R. Martin
Keyword(s):  
Normal Level ◽  
Auditory Feedback ◽  
Concomitant Increase ◽  
Vocal Intensity ◽  
Presence And Absence

The present study was designed to assess the effects of increased vocal level on stuttering in the presence and absence of noise, and to assess the effects of noise on stuttering with and without a concomitant increase in vocal level. Accordingly, eight adult stutterers spoke in quiet with normal vocal level, in quiet with increased vocal level, in noise with normal level, and in noise with increased level. All subjects reduced stuttering in noise compared with quiet conditions. However, there was no difference in stuttering when subjects spoke with normal compared with increased vocal level. In the present study, reductions in stuttering under noise could not be explained by increases in vocal level. It appears, instead, that reductions in stuttering were related to a decrease in auditory feedback. The condition which resulted in the largest decrease in auditory feedback, speaking in noise with a normal level, also resulted in the largest decrease in stuttering.

Sign in / Sign up

Export Citation Format

Share Document