Initiation of cardiac differentiation occurs in the absence of anterior endoderm

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2439-2450 ◽  
Author(s):  
M. Gannon ◽  
D. Bader
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
Cardiac Differentiation ◽  
Specific Gene ◽  
Lateral Plate ◽  
Sarcomeric Protein ◽  
Cardiac Gene Expression ◽  
Stage 4 ◽  
Short Period ◽  
Cardiac Gene

Anterior endoderm has been proposed to be a specific inducer of cardiac differentiation in vertebrates (reviewed in Jacobson and Sater, Development 104, 341–359, 1988). The ability of cardiogenic mesoderm to differentiate in a minimal culture system was examined using cardiac-specific gene expression as an assay. Anterior lateral plate mesoderm was explanted from chick embryos with and without associated endoderm at developmental stages from just after gastrulation (stage 4; Hamburger and Hamilton, J. Morph. 88, 49–67, 1951) to just prior to contraction (stage 9). At all stages examined, cardiogenic mesoderm expressed a profile of cardiac-specific mRNAs after two days in minimal medium independent of the presence of endoderm. Our studies indicate that endoderm is necessary for the generation of stable sarcomeric protein expression, organized myofibrils and beating tissue from stage 4–6. Subsequent to this stage, an interaction with anterior endoderm is no longer required. Examination of cardia bifida embryos from which anterior endoderm had been unilaterally removed also showed a stage-dependent effect of endoderm on beating, while cardiac gene expression and heart morphogenesis were unaffected. These results demonstrate that anterior endoderm does not induce or maintain cardiac gene expression, nor is it required for terminal differentiation. Endoderm does appear to be necessary for a short period of time between initiation of cardiac gene expression and the onset of contraction.

Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8 (fgf8/acerebellar)

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 225-235 ◽  
Author(s):  
F. Reifers ◽  
E.C. Walsh ◽  
S. Leger ◽  
D.Y. Stainier ◽  
M. Brand
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Lateral Plate ◽  
Direct Function ◽  
Fibroblast Growth Factor 8 ◽  
Extracellular Signals ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Cardiac Precursor Cells ◽  
Zebrafish Heart

Vertebrate heart development is initiated from bilateral lateral plate mesoderm that expresses the Nkx2.5 and GATA4 transcription factors, but the extracellular signals specifying heart precursor gene expression are not known. We describe here that the secreted signaling factor Fgf8 is expressed in and required for development of the zebrafish heart precursors, particularly during initiation of cardiac gene expression. fgf8 is mutated in acerebellar (ace) mutants, and homozygous mutant embryos do not establish normal circulation, although vessel formation is only mildly affected. In contrast, heart development, in particular of the ventricle, is severely abnormal in acerebellar mutants. Several findings argue that Fgf8 has a direct function in development of cardiac precursor cells: fgf8 is expressed in cardiac precursors and later in the heart ventricle. Fgf8 is required for the earliest stages of nkx2.5 and gata4, but not gata6, expression in cardiac precursors. Cardiac gene expression is restored in acerebellar mutant embryos by injecting fgf8 RNA, or by implanting a Fgf8-coated bead into the heart primordium. Pharmacological inhibition of Fgf signalling during formation of the heart primordium phenocopies the acerebellar heart phenotype, confirming that Fgf signaling is required independently of earlier functions during gastrulation. These findings show that fgf8/acerebellar is required for induction and patterning of myocardial precursors.

scholarly journals Calcium handling precedes cardiac differentiation to initiate the first heartbeat

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Richard CV Tyser ◽  
Antonio MA Miranda ◽  
Chiann-mun Chen ◽  
Sean M Davidson ◽  
Shankar Srinivas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Contractile Function ◽  
Rapid Development ◽  
Mouse Embryos ◽  
Cardiac Differentiation ◽  
Calcium Handling ◽  
Heart Tube ◽  
Cardiac Gene Expression ◽  
Stage Of Development ◽  
Cardiac Gene

The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca2+-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8.0 and was associated with sarcomeric assembly and rapid Ca2+ transients, underpinned by sequential expression of the Na+-Ca2+ exchanger (NCX1) and L-type Ca2+ channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca2+ handling in the early heart and an essential early role for NCX1 in establishing SACOs through to the initiation of beating. NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation.

scholarly journals Doppler Echocardiographic Assessment and Cardiac Gene Expression Analysis of the Left Ventricle in Myocardial lnfarcted Rats

1998 ◽  
Vol 62 (6) ◽  
pp. 436-442 ◽  
Author(s):  
Naruhito Shimizu ◽  
Minoru Yoshiyama ◽  
Kazuhide Takeuchi ◽  
Akihisa Hanatani ◽  
Shokei Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Echocardiographic Assessment

scholarly journals Myocardin Marks the Earliest Cardiac Gene Expression and Plays an Important Role in Heart Development

2008 ◽  
Vol 291 (10) ◽  
pp. 1200-1211 ◽  
Author(s):  
Jian-Fu Chen ◽  
Shusheng Wang ◽  
Qiulian Wu ◽  
Dongsun Cao ◽  
Thiha Nguyen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

Abstract 289: Transcriptomic Analysis of Inter- and Intra-patient Variation in Human iPSCs: Platform for Precision Medicine to Predict Drug Toxicity

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Elena Matsa ◽  
Paul W Burridge ◽  
Kun-Hsing Yu ◽  
Haodi Wu ◽  
Vittavat Termglinchan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Precision Medicine ◽  
Disease Modeling ◽  
Sendai Virus ◽  
Expression Profiles ◽  
Cardiac Differentiation ◽  
Patient Specific ◽  
Specific Gene ◽  
Drug Induced ◽  
Human Ipscs

Rapid improvements in human induced pluripotent stem cell (hiPSC) differentiation methodologies have allowed previously unattainable access to high-purity, patient-specific cardiomyocytes (CMs) for use in disease modeling, cardiac regeneration, and drug testing. In the present study, we investigate the ability of hiPSC-derived cardiomyocytes (hiPSC-CMs) to reflect the donor’s genetic identity and serve as preclinical functional readout platforms for precision medicine. We used footprint-free Sendai virus to create two separate hiPSC clones from the fibroblasts of five different individuals lacking known mutations associated with cardiovascular disease. Whole genome expression profiling of hiPSC-CMs showed that inter-patient variation was greater than intra-patient variation, thereby verifying that reprogramming and cardiac differentiation technologies can preserve patient-specific gene expression signatures. Gene ontologies (GOs) accounting for inter-patient variation were mostly metabolic or epigenetic. Toxicology analysis based on gene expression profiles predicted patient-specific susceptibility of hiPSC-CMs to cardiotoxicity, and functional assays using drugs targeting key regulators in pathways predicted to produce cardiotoxicity showed inter-patient differential responses in hiPSC-CMs. Our data suggest that hiPSC-CMs can be used in vitro to predict and help prevent patient-specific drug-induced cardiotoxicity, potentially enabling personalized patient consultation in the future.

Abstract 247: Scaffold-stiffness Dependent Notch1 Activation Regulates Cardiogenic Gene Expression In Cardiac Progenitor Cells

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Archana V Boopathy ◽  
Pao L Che ◽  
Yoshie Narui ◽  
Khalid Salaita ◽  
Michael E Davis
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Adult Stem Cells ◽  
Cardiac Progenitor Cells ◽  
Critical Pathway ◽  
Cardiac Gene Expression ◽  
Self Assembling ◽  
Cardiac Gene

Rationale: Cardiac progenitor cells (CPCs) are multipotent, self-renewing cells that can regenerate the myocardium and improve cardiac function in animal models of myocardial infarction (MI). However, limited survival of stem/progenitor cells inhibits cardiac regeneration. Force dependent Notch activation promotes cardiac development and cardiac gene expression in many adult stem cells. As dysregulation of Notch signaling leads to embryonic lethal cardiovascular defects, activating this critical pathway during cell transplantation could improve efficacy of stem cell therapy. Objective: Investigate i) whether self-assembling peptide scaffolds can be used to activate Notch1 signaling in CPCs to promote cardiogenic differentiation and ii) the effect of scaffold stiffness on Notch1 activation and differentiation. Methods: Rat CPCs (c-kit + ) were cultured for 48h in 3D self-assembling scaffolds of varying stiffness (1% low, 2% high): empty scaffolds (RADA), scaffolds modified with peptide mimicking Notch1 ligand, Jagged1 (RJAG), or scaffolds modified with a scrambled peptide (RSCR) and cardiogenic gene expression measured by qRT-PCR. CHO cells expressing Notch1 responsive YFP were also cultured in the above scaffolds for 48h and YFP expression was determined. Results are mean ± SEM with p<0.05 considered significant by one or two-way ANOVA with appropriate post test. Results: In the Notch1 reporter cells, Notch1 activation increased significantly in presence of RJAG (p<0.01) and on increasing scaffold stiffness (p<0.01,n=6) indicating scaffold stiffness-dependent Notch1 activation. Culture of CPCs in RJAG containing 1% scaffolds (low stiffness) significantly increased early endothelial and smooth muscle but not cardiac gene expression while in 2% scaffolds (high stiffness) significantly increased only cardiac and not endothelial or smooth muscle gene expression (p<0.05, n≥4). Conclusions: Taken together, these data show that i) Notch1 activation in 3D is dependent on ligand density and scaffold stiffness and ii) stiffness dependent Notch1 activation differentially regulates cardiogenic gene expression in CPCs. Therefore, delivery of CPCs in JAG containing scaffolds could be used to improve cardiac function following MI.

scholarly journals Corrigendum to “Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis” [Dev. Biol. 297 (2006) 566–586]

2007 ◽  
Vol 309 (2) ◽  
pp. 386
Author(s):  
Allesandro D. Mori ◽  
Yonghong Zhu ◽  
Ilyas Vahora ◽  
Brian Nieman ◽  
Kazuko Koshiba-Takeuchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Gene Expression ◽  
Cardiac Gene

Multifactorial Regulation of Cardiac Gene Expression: an In Vivo and In Vitro Analysis

1995 ◽  
Vol 752 (1 Cardiac Growt) ◽  
pp. 370-386 ◽  
Author(s):  
J. L. SAMUEL ◽  
I. DUBUS ◽  
F. FARHADIAN ◽  
F. MAROTTE ◽  
P. OLIVIERO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Vitro Analysis ◽  
In Vitro Analysis
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