Asymmetry is crucial for the heart proper functioning, and now, scientists from the Institute Gulbenkian of Science in Portugal and Harvard University, have discovered that a family of genes, called Nodal, is crucial determining this asymmetry by controlling the speed and direction of the heart muscle cells during embryonic development. The finding, by helping to understand how the heart develops, is a step closer to intervene and is of particular importance if we consider that problems in heart asymmetry are the main cause of heart congenital diseases that can affect as much as 8 out of 1000 newborns. The research will appear in a special December issue of the journal Development Dynamics 1 dedicated to left-right asymmetry development.
At first glance, the left and right sides of our bodies are identical to one-another. Inside, however, it is quite a different story and organ asymmetry is believed to improve not only the packaging of the organs, but also their proper functioning. The normal disposition of internal organs and structures, which is conserved within vertebrates, is called situs solitus. Alterations of this state include full mirror-reversal organ disposition- a pathology made famous by news of people stabbed in the heart just to discover that their heart was in fact on the opposite side of the body - or cases where individuals have two right or two left sides. But, despite the fact that most alterations in the normal positioning of human organs originate severe medical conditions, very little is actually known about the events behind this type of development. As such, to understand them is not only a fundamental question of Developmental Biology but also highly relevant for human health. This is of particular importance with the heart, which is incredible susceptible to any changes in its normal asymmetry, as the high mortality and disease rates in patients with congenital heart defects so clearly demonstrate.
With this in mind Maria Ines Medeiros de Campos-Baptista and Alexander F. Schier from the Institute Gulbenkian of Science (Lisbon, Portugal) and the Harvard University (Cambridge, USA) and colleagues decided to analyse the expression of the Nodal gene family – which has been linked to left-right axis determination in vertebrates - during the development of zebrafish heart.
Genes linked to asymmetric development are active in the embryo very early during development and only on one side and in fact, the researchers found that some Nodal were expressed at the onset of asymmetry, on left side of the embryo and even co-localizing with heart markers supporting the idea that this family was in fact involved in the asymmetric development of the heart.
To investigate this further Campos-Baptista, Schier and colleagues used a powerful 4D microscope technique that allows to follow individual cells, to film, in real time, the heart development of zebrafish embryos that have been modified to express green fluorescent protein (GFP) in their heart muscle cells (or cardiomyocytes). The idea was that with this marker - together with the fact that zebrafish embryos are transparent - it was possible to track of individual cardiomyocytes as the heart developed to determine the importance of Nodal genes in this development. By comparing animals with or without functional Nodal, the researchers found that these genes regulated the speed and direction of cardiomyocytes, and, when lacking, led to slower and randomly moving cardiomyocytes that losing their asymmetric behaviour, go and form a symmetrically positioned heart (so localised on the body midline).
Nevertheless, although problems in the Nodal genes do affect heart positioning, the fact that this organ is still formed and the organism is viable – although probably not too healthy - reveals that other independent mechanisms, regulated by other genes, affect the same development.
In conclusion, Campos-Baptista, Schier and colleagues’ results show that the movement of individual cardiomyocytes is the determining force behind heart morphogenesis, and that the Nodal genes, by controlling the speed and direction of individual heart muscle cells, are in fact responsible for the asymmetric formation of the heart
“The next step - according to Ines Campos-Baptista, a Portuguese researcher and the first author of the article - will be to identify other genes this time behind the particular movements of the cardiac cells, such as those linked to the cell skeleton, etc. Identifying these will be crucial to fully understand heart asymmetric formation and - since Nodal also plays a role in this developmental of other organs - it will also shed light on the development of many other internal organs such as the pancreas, gut, lungs, etc.”
Campos-Baptista, Schier and colleagues’ findings are important for a better understanding of the mechanism behind embryonic development., specifically of the heart, and, as such, can take us a little closer to one day to be able, not only of preventing heart congenital anomalies, but also of being able to grow our own heart tissues. Although that time is still a long, long way away.
Piece by Catarina Amorim (catarina.amorim at linacre.ox.ac.uk)
Catarina Amorim | alfa
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences