Fate switch

Why a twist of fate helps re-grow lost body parts

If you cut a limb from a tree, the tree can grow a new one. Why can't humans do the same?

Why some organisms, such as plants, have the ability to regenerate missing body parts while others, such as humans, do not is now being investigated by researchers at Dundee.

Dr Silvia Costa in the College of Life Sciences Division of Gene Regulation and Expression is leading the study.

"Plants are remarkable in that they can regenerate the entire organism from a small piece of tissue, or even a single cell," she said.

"An understanding of how they do this could provide us with a new perspective on regeneration in animals and maybe one day lead us to new ways for growing replacement body parts."

To understand how they do this, we must first go back to the very early stages of development when the fate of a cell is decided.

All cells in plants and animals contain all of the genetic information for the organism, but only certain genes are switched on in each cell. The "switched-on" genes determine the fate of the cell, for example, whether it is a nerve cell or muscle cell or liver cell.

This switching on of the selected sets of genes occurs in the very first days of the life of the organism and in most animals remains set for the rest of their life.

A nerve cell cannot one day become a heart cell, or a heart cell cannot change its destiny and become a cell of the skin. This maintenance of the cell's identity is an important mechanism that guarantees the integrity and functioning of the organism.

Plants however, seem to have a special trick. They can change the fate of a cell, even in an adult, by switching off genes that are currently switched on, and instead switching on new ones. So, for example, a root cell could give rise to shoot cells amd a shoot cell could give rise to root cells.

This is a very useful trick for overcoming environmental hardships that the plant might face, such as severe weather conditions that cause damage to the shoots and leaves or drought-ridden soil that increases the demand for deeper roots.

If we were to imagine the equivalent in animals, a serious car crash that leads to a severed spinal cord could see the nearby blood vessel cells, fat cells and bone cells changing their fate, becoming nerve cells and helping to rebuild the spinal nerve. But this doesn't happen.

In evolutionary terms, animals have had less of a demand than plants for replacing lost organs and are generally better able to withstand environmental conditions. Plants, on the other hand, are more sensitive to the environment and have developed strategies to overcome this.

So what are these strategies?

Dr Costa and her colleague, Professor Peter Shaw at the John Innes Centre in Norwich, think a group of proteins called PRC1 and PRC2 might be one of the keys.

PRC2 proteins exist in both animal and plant cells and are believed to play a role in determining the fate of cells, deciding which genes to switch on in the early days of life.

"Animal cells have very good memories when it comes to their fate. The genetic switches that are turned on in the first few days of life remain with the cell for the rest of its life," Dr Costa said.

Plants also have a good cellular memory - but they also maintain the ability to change it.

"As yet, nobody has been able to find PRC1 proteins in plant cells and we believe that this could be the key to unlocking the cellular memory."

So, the plant keeps a back-up plan, or "fate switch" that will enable it to change the fate of its cells if it needs to.

In this way, plant cells might be quite similar to animal stem cells, which are able to continuously perceive external stimuli and develop into the most suitable cell their environment demands.

"A possibility is that changes in fate can be accomplished faster and easier when cells replicate their DNA and divide. In fact, we know that during these processes the organisation of the chromatin, composed of the DNA and its associated proteins, is changed," Dr Costa said.

Along with Professor Julian Blow in the Division of Gene Regulation and Expression, she is investigating the interaction between the proteins controlling the cell cycle and those regulating chromatin organisation to gain a better understanding of how chromatin can be reorganised during the process of cell division.

Dr Costa hopes that her research will help to provide some clues as to why fate switch and regeneration are rare events in animals. She believes such understanding could help to find new strategies to improve regenerative capacity in adults so that one day we could rebuild our own organs when they are damaged or dying.