Viewed from the outside, our body looks completely symmetrical. However, most internal organs including the heart are formed asymmetrically. The right side of the heart is responsible for pulmonary circulation; the left side supplies the rest of the body. This asymmetry allows the heart to do its job effectively. In a study on zebrafish embryos, the researchers Dr. Justus Veerkamp and PD Dr. Salim Seyfried from the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch have now shown how the left and right sides of the heart develop differently. Their findings were published in the journal Developmental Cell (doi: http://dx.doi.org/10.1016/j.devcel.2013.01.026)*.
A protein called Nodal plays an important role in the development of asymmetry. In an early stage of heart development, Nodal is formed on the left side and triggers a multi-step signaling cascade that enables the cardiac progenitor cells on this side to migrate faster. The researchers were able to observe the migration of the cardiac progenitor cells in the zebrafish embryos in vivo. Since the embryos are transparent it is possible to view each single cell using the microscope.
While analyzing the individual proteins involved in the asymmetric development of the heart, Dr. Veerkamp and Dr. Seyfried encountered a surprise: Previously, scientists had assumed that another signaling molecule, the protein Bmp, triggered cell migration on the left side of the heart and, as a consequence, must be very active there.
Current studies, however, show just the opposite: Bmp reduces the motility of the cells that form the heart. The protein Nodal regulates this process by activating the enzyme Has2. This in turn restricts Bmp activity on the left side. Thus, the cells of the left side of the heart migrate faster and ultimately form a functional, asymmetric heart.
However, when the resear
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Helmholtz Association of German Research Centres