Although our bodies seem to be bilaterally symmetrical at a glance, the way in which our organs are stereotypically located shows they are internally typically asymmetrical, for instance, whilst the heart is located on the left hand side, the liver is on the right side. Scientists have long been interested how this inherent left-right asymmetry is established, due to its intrinsic biological importance and for medical applications.
In a study published online in the March 6 issue of the open-access journal PLoS Biology , scientists have discovered that the gut endoderm plays an important role in generating information that determines whether organs develop in the stereotypical left-right pattern.
Researchers have established, in a mouse model, that the principal event that breaks left-right symmetry occurs at a specialized organ, called the node, which is located in the midline of the developing embryo.
The key question of how this initial asymmetry at the node causes a series of events that generate laterality information to a distant location within the embryo has puzzled scientists for more than 10 years. Earlier experiments have established that these series of events cause an activation of the genetic circuit on the embryo’s left side, which eventually results in asymmetric organ formation. If the series of events does not take place, left-right asymmetry cannot be established.
According to findings by Kat Hadjantonakis, and her team at the Sloan-Kettering Institute of the Memorial Sloan Kettering Cancer Center in New York, the asymmetric signals that are generated at the node are transferred via an epithelium (the gut endoderm) residing on the embryo’s surface to the embryo’s extremity. The gut endoderm is the tissue that contains the generator cells for the epithelial lining of the respiratory and digestive tracts and its related organs like lungs, pancreas and liver.
The researchers observed that mouse embryos, without the HMG domain-containing transcription factor Sox17 , have a defective gut endoderm formation and are therefore unable to establish left-right asymmetry. They then demonstrated that the mechanism for relaying the left-right information is caused by communication amongst cells across gap junctions located within the gut endoderm epithelium.
Written by Petra Rattue