16 December 2016

How does the liver find its place in the body?

Stem cells

New research investigating how the liver finds its place in the body during development. In a recently published study, the Ober group from The Novo Nordisk Foundation Center for Stem Cell Biology at the Faculty of Health and Medical Sciences at the University of Copenhagen has demonstrated how the cells that will become the liver find their place in the body, where they fully develop the liver. The discovery helps to understand the cell movement patterns in normal development and in diseases in which organs develop in the wrong place in the body.

Organs already find their position in the embryo, which is the earliest stage of development of an organism. In the early embryo, each organ develops from a group of specific group of early-stage cells, so called progenitor cells. The cells are initially formed in the midline of the embryo and then move either to the left or to the right in order to place the organs in the body in the most efficient way. Progenitor cells must therefore be able to move, receive instructions and ultimately interact with other cells while navigating through the embryo until they reach their final destination where they fully develop the organ.

But what controls the liver progenitor cells' movement towards their final destination? To answer this question, the Ober group has studied zebrafish embryos. Zebrafish are transparent, making it possible to observe the internal organs as they develop in the living embryo. By studying the liver development of zebrafish, the researchers discovered that the progenitor cells actively migrate away from the gut, which challenges a previous hypothesis that cells on the right ‘push’ liver cells into the correct position.

Instead of pushing the cells, the researchers have demonstrated that the neighbouring cells on the right send repulsive signals to the progenitor cells telling them to move to the left. The group discovered that the progenitor cells form short and long cellular extensions, which they use to explore their surrounding space for these signals. The team showed that the signalling mechanism responsible for this cell-cell interaction is mediated by two proteins: EphrinB1 on the surface of liver progenitors and EphB3b on the surface of the neighbouring cells.

Lack of the two proteins, which are responsible for sending and receiving signals between the cells, may impair the cells' ability to move around as they should. As a result, the organs do not develop in the right place in the body. The Ober group's discovery provides an understanding of the right-left movement that organs make during their development as well as conditions such as Situs Inversus in which one or more organs are positioned opposite of normal positions.

The study has been published in the scientific journal Developmental Cell. You can read it here.

Group Leader Elke Ober, E-mail: elke.ober@sund.ku.dk, Telephone: +45 23 64 87 82