Tiny flies could lead to understanding potential for non-embryonic stem cells

[Guest guest]

Medical News Today 01 Mar 2005

Tiny flies could lead to understanding potential for non-embryonic

stem cells

It has long been thought that cells that regenerate tissue do so by

regressing to a developmentally younger state. Now two University of

Washington researchers have demonstrated that cells can regenerate

without becoming " younger. "

Biologists for years have studied stem cells, the ones responsible

for replenishing and regenerating an organism's structures, aiming to

find the means to selectively regenerate tissue such as that of the

heart or liver in much the same way that the body heals a broken leg.

Much hope rests with non-embryonic stem cells, which can renew

themselves and, within limits, produce all the specialized cell types

from the type of tissue in which they originate. But scientists have

puzzled over just how such cells function, how they can be spurred to

create new tissue, and just when in their development it is

determined what tissue they can produce.

Gerold Schubiger, a UW biology professor, and Anne Sustar, a research

technician in his laboratory, used groups of cells, called imaginal

discs, in fruit fly larvae to provide an easily controlled system to

study regeneration. Imaginal discs convert genetic information that

determines the specific tissue into which the cells will develop in

the adult fly. For example, leg discs form only adult legs and wing

discs form only adult wings. Normally, all of those cells develop

into that specific tissue, either when the fly reaches the adult

stage or when regenerating a lost structure, such as parts of a leg

disc.

The exception is a very small number of cells in each disc, located

at what the researchers term the " weak point. " These cells change

their ultimate destiny, or fate, as the disc regenerates tissue so

that, for example, instead of regenerating leg structures they form

wing structures. Such fate changes are known as transdetermination,

and they demonstrate that a few cells have development potential that

is adaptable rather than firmly fixed, Schubiger said. That has

parallels in the adaptable development potential found in some

vertebrate stem cells, he said.

In the case of the fruit flies, regeneration and transdetermination

begin in the " weak point " of the leg imaginal disc when a signaling

gene called wingless activates a selector gene called vestigial,

which spurs wing development in that stem cell-like region.

" In all organisms, selector genes activate or repress other genes

that trigger production of different organs. Researchers studying

cells with adaptable development potential want to know when, where

and how those cells change their fate, " Schubiger said.

In previous research involving vertebrates, he said, it was unclear

whether cells involved in tissue regeneration had reverted to a

younger state or were the same age as other cells in the organism.

But he noted that it has been generally accepted that the

regenerating cells revert to a younger state.

If that is true, those cells would have to divide faster than the

others in the organism because younger cells divide faster than older

cells. Sustar and Schubiger tested the theory in fruit flies,

following the cells to see when and where the vestigial gene was

activated. Since cells in the disc divide more slowly as they age,

the researchers could see whether the cells involved in regeneration

had reverted to a younger cycle. They found that neither cells

involved in regeneration nor those that were changing their fate to

become a different type of tissue had the characteristics, including

the faster doubling time, of younger cells.

Sustar is the lead author of a paper describing the work, published

in the Feb. 11 edition of the journal Cell. The work was supported by

a grant from the National Institutes of Health.

Understanding the wingless gene's function is key to understanding

how stem cells can adapt their ultimate destiny, from leg tissue to

wing tissue for example, Schubiger said.

There are many examples in which the wingless gene causes stem cells

to change fates, he added. In hair follicle cells, for example, the

wingless gene changes stem cells to skin cells. In a mouse, high

levels of wingless genes change a specific group of lung cells into

intestine cells.

" This work challenges old concepts of regeneration and has opened new

avenues for stem cell research, " Schubiger said. " This remarkable

observation has not been reported in any stem cell research. We have

set the stage to look at the cell cycle in other stem cell systems. "