Normal Development Of Cells With Abnormal Numbers Of Nuclei

These cells, which are known as binucleated tetraploid hepatocytes, arise in all mammals as a result of failure of the cellular process cytokinesis (the process by which the bulk of a cell, excluding the nucleus, divides to form two "daughter" cells). New insight into the failure of this process has now been provided by Chantal Desdouets and colleagues, at Institut Cochin, France, who have identified a cellular signaling pathway that leads to cytokinesis failure and the formation of binucleated tetraploid hepatocytes in rodents.

Initial analysis revealed that weaning triggered the initiation of cytokinesis failure and formation of binucleated tetraploid hepatocytes in rats. Follow up studies in mice and rats indicated that the aspect of the suckling-to-weaning transition that controls the initiation of cytokinesis failure is the increase in insulin levels that occurs upon weaning.

Further in vitro analysis, using pharmacological inhibitors, determined the signaling pathway by which insulin controlled cytokinesis failure.

Future studies will investigate whether the deregulation of the insulin signaling pathway observed in various metabolic diseases alters the number of binucleated tetraploid hepatocytes in the liver ploidy profile and whether this has a role in disease.