Breaking News
September 19, 2018 - Inequality issues persist even under new U.S. kidney transplant allocation system
September 19, 2018 - New study reveals mechanisms that lead to cognitive decline in Type 2 diabetes
September 19, 2018 - FDA launches new comprehensive effort to educate kids about dangers of e-cigarettes
September 19, 2018 - Study reveals mechanism underlying plants’ ability to signal defense
September 19, 2018 - Researchers harness Zika virus vaccine under development to target glioblastoma
September 19, 2018 - Novel deep learning drug discovery platform gets £1 million innovation boost
September 19, 2018 - Sensor array may detect de novo Parkinson’s disease in breath
September 19, 2018 - A roadmap for the future of electronic health records
September 19, 2018 - Surprising research showing peptide adaptability may pave way to develop immunotherapies
September 19, 2018 - Amyloid β protein makes comeback as therapeutic target for Alzheimer’s disease
September 19, 2018 - Alcon expands its global support of eye care professionals through Alcon Experience Academy
September 19, 2018 - Study gives new insights into how cells leverage GPCRs to control inflammation
September 19, 2018 - Automatic relevance detection in ophthalmic surgery videos
September 19, 2018 - UNIST to accelerate discovery, development of new medicines for incurable diseases
September 19, 2018 - Novel clinical trial to examine cannabis as potential treatment for essential tremor
September 19, 2018 - Salsa dancers have lower injury rates than Spanish, aerobic or Zumba dancers
September 19, 2018 - Bristol-Myers Squibb’s Novel, Oral, Selective TYK2 Inhibitor Delivered Significant Skin Clearance in Patients with Moderate to Severe Plaque Psoriasis in Phase 2 Trial
September 19, 2018 - Can work stress contribute to Parkinson’s disease risk?
September 19, 2018 - Global Climate Action Summit: A focus on kids and climate
September 19, 2018 - Vitamin D may reduce breast cancer mortality in women with lower BMI
September 19, 2018 - Targeted Lung Denervation procedure significantly reduces COPD problems
September 19, 2018 - FDA-approved ‘safe’ daily BPA exposure may contribute to insulin resistance
September 19, 2018 - Research finds physical connection between the brain’s fluid reservoirs and meningeal lymphatics
September 19, 2018 - UCalgary study could help physicians make better treatment decisions for stroke
September 19, 2018 - Biomedical review finds failure rates in some surgical mesh treatments to be unacceptably high
September 19, 2018 - Researchers develop more accurate measure of body fat
September 19, 2018 - Doctors and students rally to support gun violence research, education
September 19, 2018 - LEO Pharma and MorphoSys announce expansion of strategic alliance to develop peptide-derived drugs
September 19, 2018 - Seniors in pain hop aboard the canna-bus
September 19, 2018 - New compound could prevent malaria parasites from maturing inside mosquito
September 19, 2018 - Scientists find alterations in blood flow in response to body position change
September 19, 2018 - UNC Health Care extends free access to virtual care service in the aftermath of Hurricane Florence
September 19, 2018 - Opioid Refills Rare After Rhinoplasty
September 19, 2018 - Corn, obesity, and navigating healthy eating choices as a parent
September 19, 2018 - Journal editor aims to prompt thoughtful review of ethics in precision health
September 19, 2018 - Researchers identify key step in how plant cells respond to pathogens
September 18, 2018 - Researchers analyze how exposure to silver nanoparticles affects zebrafish
September 18, 2018 - Study shows air pollution may be bad for the fetus
September 18, 2018 - Coffee May Have Another Perk for Kidney Patients
September 18, 2018 - Tongue-in-cheek Nobels honor nutritional analysis of cannibalism, roller-coaster kidney stones treatment
September 18, 2018 - Progress, priorities, challenges are focus of State of Stanford Medicine | News Center
September 18, 2018 - Established Alzheimer’s Risk Gene Has a New Role
September 18, 2018 - Hospitalization after antibiotic initiation found to be higher for people with Alzheimer’s disease
September 18, 2018 - Many children with special healthcare needs do not have access to ‘PCMH-concordant’ care
September 18, 2018 - Investigational nasal influenza vaccine tested in children and teens
September 18, 2018 - Lymphatic vessels surrounding the brain play crucial role in multiple sclerosis, research suggests
September 18, 2018 - New fiber laser-based ultrasound sensor may have potential applications in medical diagnostics
September 18, 2018 - Protect your heart and health during ‘dog days’ of summer
September 18, 2018 - Faculty receive awards for promise in biomedical research, clinical care | News Center
September 18, 2018 - Digital games for CVD-related self-management improve exercise capacity and energy expenditure
September 18, 2018 - Aluminum inclusions help enhance adsorption of chemo drugs onto active carbon delivery capsule
September 18, 2018 - Adding PET scans to CT imaging can change treatment for women with cervical cancer
September 18, 2018 - UCSF awarded $20 million grant to study impacts of new, emerging tobacco products
September 18, 2018 - Human brains may be wired to prefer lying on the couch, suggests research
September 18, 2018 - Zika virus vaccine shows promise for treatment of fatal glioblastoma
September 18, 2018 - Theravance Biopharma and Mylan to Report New Data from Phase 3 Studies of Yupelri (revefenacin) in Oral Presentation at European Respiratory Society International Congress 2018
September 18, 2018 - INSiGHT identifies unique retinal regulatory genes
September 18, 2018 - Diversity, science leadership grants awarded to student-faculty pairs | News Center
September 18, 2018 - Many parents blame electronics for sleep problems among teens
September 18, 2018 - Researchers study neuronal activity in brain that prevents individuals from doing physical activity
September 18, 2018 - Purifying Proteins from Mammalian Cell Culture
September 18, 2018 - Researchers map 3D structure of toxic proteins used by Pseudomonas aeruginosa to trigger infection
September 18, 2018 - Outcome of ACL reconstruction related to the way you move post-surgery
September 18, 2018 - Study aims to investigate risk factors for PPCs in surgical patients with gastric cancer
September 18, 2018 - Ardelyx Submits New Drug Application for Tenapanor for IBS-C
September 18, 2018 - Sociodemographic disparities in eyeglass use among elderly
September 18, 2018 - New Drug Shows Promise for Progressive Form of MS
September 18, 2018 - Babies exposed to higher levels of organochlorine compounds in womb may have worse lung function
September 18, 2018 - Women exposed to trauma in their lives gave birth to underweight male infants
September 18, 2018 - Probiotic supplementation may reduce use of antibiotics, scientific analysis shows
September 18, 2018 - Resveratrol decreases pain severity and levels of inflammatory biomarkers in osteoarthritis patients
September 18, 2018 - Research shows pollution is reaching the placenta
September 18, 2018 - KAIST researchers develop heart-targeting drug delivery technology using tannin acid
September 18, 2018 - Muscle relaxants used during general anesthesia can increase risk of pulmonary complications
September 18, 2018 - Silicone breast implants may increase risk of rare adverse outcomes in women
September 18, 2018 - Pediatricians Have a Role in Encouraging Play Among Children
September 18, 2018 - California’s Medicaid program hits ‘print’ when the feds need info
September 18, 2018 - Genes, environment and schizophrenia—new study finds the placenta is the missing link
September 18, 2018 - Boehringer Ingelheim announces study results of COPD patients treated with Spiolto Respimat
September 18, 2018 - PAREXEL launches Patient Innovation Center to improve drug development process
Polarized cells give the heart its fully developed form

Polarized cells give the heart its fully developed form

image_pdfDownload PDFimage_print
An explanted zebrafish heart loops on its own in a petri dish (left), but without the Frizzled-7a factor necessary for Planar Cell Polarity signaling, it remains tubular (right). Credit: Anne M. Merks, MDC

When it first starts to develop, the heart is a simple tube. Reporting in the journal Nature Communications, researchers at MDC have now described how it forms itself into a its characteristic S-shape and how the ventricles and atria finally develop. Their findings will help scientists to better understand the development of congenital heart diseases.

In Germany, nearly one child in 100 is born with a heart defect. Until recently, little was known about the causes of congenital heart disease. But now important new insights have been provided by research on embryonic heart development by an international team led by Dr. Daniela Panáková, leader of the Electrochemical Signalling in Development and Disease working group at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin.

By conducting experiments with zebrafish, Panáková and her colleagues at MDC and the universities of Potsdam and Zürich have identified the mechanisms by which the heart takes on its fully developed form. Their study was published together with another article on early heart development in the zebrafish in the same issue of Nature Communications. In this paper, a team led by Prof. Christian Mosimann from the Institute of Molecular Life Sciences at the University of Zürich, with the participation of Panáková’s team, reports how the heart first develops into a tube-like form through the continuous flow of heart precursor cells.

Heart cells must find new neighbours

“We then turned to the question of how the linear tube loops round into the characteristic S-shape, which ultimately goes on to form the ventricle and the atrium of the zebrafish heart,” says one of the study’s two lead authors, Anne Margarete Merks from Panáková’s lab. “For this process to occur, the second-generation heart cells need to integrate into the linear heart and identify their correct place.” She explains that this involves relocations of the cells. “They change their neighbours and find new cells to share the cell boundaries with,” says Merks.

As she and her colleagues report, this process is controlled by a signalling pathway—a chain of chemical reactions that cause the cells to react to external signals—known as the PCP signalling pathway. PCP stands for ‘planar cell polarity’. Two components are especially important to this pathway: the molecules Fzd7a and Vangl2. “When we deactivated the genes for these molecules in zebrafish, the heart was unable to develop properly,” says Merks. “Clearly, the cells were unable to locate their future neighbours.”

Polarized cells give the heart its fully developed form
Heart cells of a zebrafish embryo find new neighbors. Over a course of five hours, five heart muscle cells initially sharing a common cell boundary form a new cell junction (arrow/arrowhead). Credit: Marie Swinarski, MDC

Tissue tension is crucial

The PCP signalling pathway influences not just individual cells but also the tissue as a whole. “If the signalling pathway is disrupted in some way, the tissue tension changes,” says Merks. Without the correct tension, the looping process cannot take place and the formation of the heart is impaired. As the researchers discovered in further experiments, the change in tissue tension is due to the fact that the defective PCP signalling pathway alters the cytoskeleton of the heart muscle cells. The cytoskeleton consists of the proteins actin and myosin and enables muscle cells and therefore an entire muscle to contract.

“Normally we observe that the cytoskeleton in the heart cells doesn’t look the same everywhere, but exhibits polarity,” explains Merks. “The surface of the cells differ from their base.” If the PCP signalling pathway is disrupted, this polarity is lost. As a result, the tube-shaped heart cannot take on its new form properly. “The outflow tract, in particular, is unable to develop correctly,” Merks explains. Most congenital heart diseases are due to problems in this part of the organ.

Results transferable to humans

Merks and her colleagues carried out their experiments on zebrafish, because these animals have the important advantage that the heart develops very quickly and starts to beat just 24 hours after fertilisation. “But we’re confident that our findings can be transferred to mammals, including humans,” says Panáková. “The PCP signalling pathway is highly conserved in evolutionary terms and the genes involved in it have already been identified in humans and associated with congenital heart disease.”

Next, Panáková and her team are planning to carry out studies with heart tissue from patients with the congenital heart diseases tetralogy of Fallot and DORV (double outlet right ventricle). They will source the tissue from a biobank run by the Competence Network for Congenital Heart Defects. Through their experiments, the researchers at MDC aim to identify exactly to what extent a disrupted PCP signalling pathway is implicated in the development of these diseases.


Explore further:
Zebrafish heart development reveals key insight into inherited heart defects

More information:
Anne Margarete Merks, et al. (2018): “Planar cell polarity signalling coordinates heart tube remodelling through tissue-scale polarisation of actomyosin activity.” Nature Communications. DOI: 10.1038/10.1038/s41467-018-04566-1

Journal reference:
Nature Communications

Provided by:
Max Delbrück Center for Molecular Medicine

Tagged with:

About author

Related Articles