JUN 04, 2018 11:57 AM PDT

What the Zebrafish Heart Says About Congenital Heart Defects

WRITTEN BY: Kara Marker

Heart defects are the most common congenital defect, yet scientists still struggle to understand why they occur. A new study from the Max Delbruck Center for Molecular Medicine investigates a signaling pathway in the developing heart that works similarly in both zebrafish and humans.

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

To learn more about what causes congenital heart defects, scientists often study embryonic heart development: looking at how the heart develops to understand what goes wrong and identifying what mechanisms are necessary for healthy development. Additionally, scientists often conduct experiments with zebrafish, which have unique regenerative abilities.

In the newest study, scientists looked at the progression of heart development in zebrafish as it forms into a linear tube-like form, then its characteristic “S-shape,” and then into atria and ventricle chambers.

"For this process to occur, the second-generation heart cells need to integrate into the linear heart and identify their correct place," explained lead author Anne Margarete Merks. "They change their neighbors and find new cells to share the cell boundaries with."

Merks says that this process requires a constant influx of heart precursor cells, the cells that eventually development into full-fledged heart muscle cells, called cardiomyocytes. Researchers found that this process is largely regulated by the PCP (planar cell polarity) signaling pathway, particularly molecules Fzd7a and Vangl2. When these two molecules were genetically deactivated, the zebrafish heart could not develop correctly. In Merks’ words: “clearly, the cells were unable to locate their future neighbors.”

"The PCP signaling 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,” explained team leader Dr. Daniela Panakova. This evolutionary conservation is vital for the results of their studies to translate into meaningful conclusions for human congenital heart disease.

Researchers found that when the PCP signaling pathways malfunctions, whole tissues are affected. Specifically, changing tissue tension inhibits formation of the heart. Tissue tension change is caused by PCP alteration of the cytoskeleton in cardiomyocytes. The cytoskeleton contains two key proteins for contracting muscles: actin and myosin.

Normally, the cytoskeleton exhibits polarity, but malfunction of the PCP signaling pathway destroys polarity, leading to the inhibition of proper heart development. Merks says that the loss polarity affects the “outflow tract” in particular, a developing organ most often associated with congenital heart disease.

Going forward, scientists from the present study plan to apply their current findings to studies with human heart tissue donated by patients with congenital heart disease. Potentially, identifying changes in the PCP signaling pathway could one day help scientists intervene early or prevent congenital heart defects all together.

The present study was published in the journal Nature Communications.

Sources: Max Delbruck Center for Molecular Medicine in the Helmholtz Association

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
MAY 01, 2018
Health & Medicine
MAY 01, 2018
Older Adults Stick to Fitness Classes Grouped by Age
Starting and sticking with an exercise routine is difficult. If you're getting in shape after not being active, going back to the gym can be discouragi...
JUN 05, 2018
Cardiology
JUN 05, 2018
Your Heart and Your Sleeping Habits
Getting enough sleep is good for you. Old news, right? A new study from the American Academy of Sleep Medicine expands on this generic health advice, findi...
JUN 17, 2018
Cardiology
JUN 17, 2018
Microtubule Intervention to Reverse Heart Disease
Changes in the cellular structure of heart muscle cells have a large impact: past and present studies show that these types of changes can lead to heart fa...
JUN 23, 2018
Videos
JUN 23, 2018
In Search of Genetic Risk Factors for AFib
Researchers at Mass General have recently learned more about genetic factors that are contributing to a person's risk of developing AFib....
JUL 10, 2018
Genetics & Genomics
JUL 10, 2018
Reducing Cholesterol with Gene Editing
Patients with a severe kind of heart disease can't always take a drug that keep their cholesterol in check....
AUG 23, 2018
Cardiology
AUG 23, 2018
A Faster and Safe Heart Attack Diagnosis
A new clinical score can diagnose heart attack quickly and safely compared to traditional diagnostic methods....
Loading Comments...