How to fold a heart
An embryo’s heart begins as a sheet of cells that folds in complex ways as it grows. The sheet has to be tightly sealed to protect the organ, and each cell develops polarity – differences between the sides that face into and out of the heart. Salim Seyfried’s lab at the MDC and their collaborators at the University of California, Los Angeles, have now made the surprising discovery that a protein which pumps sodium out of cells also helps establish their polarity and glue them together. Without this molecule, the tissue misfolds and a heart never develops. The work appears in the Jan. 15 issue of the Journal of Cell Biology.
PhD student Elena Cibrián-Uhalte and her colleagues in Seyfried’s group have been working with the zebrafish, which is ideal for studying heart development. The fish embryo is transparent, permitting a direct look at its internal organs. It is also so small that it can absorb nutrients directly from water and can thus survive several days even if its heart is missing or malformed.
The scientists made a surprising discovery while investigating the sodium pump, a protein which helps maintain the ion balance between cells and their surroundings. When a change is needed in the cell’s electrical charge, or its levels of sodium or potassium, the molecule pumps charged particles through the membrane. In the heart, this causes muscles to contract and create a regular pattern of heartbeats. The pump also has other functions, such as helping to organize fibers and other structures that change the cell’s shape.
Zebrafish embryos without the sodium pump never developed a functioning heart because the sheet of tissue folded too slowly and took on the wrong shape. The pump was probably changing the structure or activities of single cells, but how? The group had seen the same problem before, caused by defects in other proteins. In those cases cells were unable to develop polarity – they failed to create differences between their upper and lower sides. The sodium pump might be having the same effect. If so, it would be a surprise because it would be the first time a sodium pump had been linked to the maintenance of cell polarity.
To prove this was happening, the scientists created special versions of the pump that blocked some of its tasks. Some had no effect, but any change that stopped its pumping activity led to a misfolded heart. A close look at the tissue showed that some of the seals between cells had weakened. Most importantly, the cells were no longer properly polarized. This means that the sodium pump has acquired another crucial job: as it coordinates the activity of cells, it changes their structure. In doing so, it organizes tissues and helps fold them into a heart.
Russ Hodge
Highlight Reference:
Journal of Cell Biology, Jan 15, 2007; 176, 2
Involvement of zebrafish Na+,K+ ATPase in myocardial cell junction maintenance
Elena Cibrián-Uhalte,1 Adam Langenbacher,2 Xiaodong Shu,2 Jau-Nian Chen,2,3,4,5 and Salim Abdelilah-Seyfried1,5
1 Max Delbrück Center for Molecular Medicine, 3125 Berlin, Germany
2 Department of Molecular, Cell, and Developmental Biology,
3J onsson Comprehensive Cancer Center, and
4 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095
5 Corresponding authors salim@mdc-berlin.de or chenjn@mcdb.ucla.edu
background information about the sodium pump protein
A recent related paper from the Seyfried group
full pdf version of the article
homepage of the Journal of Cell Biology
