Key Player In Embryonic Muscle Development Discovered

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Key Player In Embryonic Muscle Development Discovered

http://www.sciencedaily.com/releases/2007/04/070411152819.htm

Muscle fibers are large cells that contain many nuclei. They begin,

like all animal cells, as naive embryonic cells. These cells

differentiate, producing intermediate cells called myoblasts that

are now destined to become muscle. New myoblasts then seek out other

myoblasts, and when they find each other, they stick together like

best friends. In the final stage of muscle fiber development, the

cell membranes of attached myoblasts open up and fuse together,

forming one large, unified cell.

How myoblasts identify other myoblasts and how they cling together

had been established, but the way that the cell membranes fuse into

one has remained a mystery. Now, a study by Weizmann Institute

scientists has shed light on this mystery. The study was carried out

by research student Rada Massarwa and lab technician Shari Carmon

under the guidance of Dr. Eyal Schejter and Prof. Ben-Zion Shilo of

the Institute's Molecular Genetics Department, with help from Dr.

Vera Shinder of the Electron Microscopy Unit.

The cells' system for identifying other myoblasts and sticking to

them consists of protein molecules that poke through the outer cell

membrane -- one end pointing out and the other extending into the

body of the cell. These recognition proteins anchor the cells

together, but what makes myoblasts open their doors to each other

and merge into one cell?

The scientists discovered that a protein called WIP, which attaches

to the internal part of the myoblast recognition protein, plays a

key role in muscle cell fusion. WIP communicates between the

recognition protein and the cell's internal skeleton, which is made

of tough, elastic fibers composed of a protein called actin. The

skeletal actin applies force to the abutting cell membranes, opening

and enlarging holes that allow the cells to merge. The Weizmann

Institute team found that the WIP protein is activated by an

external signal once myoblasts identify and attach to each other.

Only when it receives this signal does WIP hook the actin fibers in

the skeleton up to the myoblast recognition protein, allowing cell

fusion to proceed.

The WIP protein has been conserved evolutionarily. In other words,

versions of it exist in all animals, from microorganisms such as

yeast, through worms and flies, and up to humans. This means that

the protein fulfills a function necessary for life but also, say the

scientists, because of this conservation, studies conducted on this

protein in fruit flies can teach us quite a bit about how it works

in humans.

To further examine the role of WIP, the scientists knocked out the

gene responsible for producing it in fruit flies. In flies that did

not make the protein, normal muscle fibers were not produced. WIP-

deficient myoblasts continued to identify and cozy up to one

another, but fusion between cell membranes did not take place, and

multi-nucleated muscle fibers failed to form. An article describing

these findings appears in the April 2007 issue of the journal

Developmental Cell.

This study, which improves our understanding of the process of

muscle formation, may assist in the future, in devising new and

advanced methods for healing muscle. Specifically, these might

include ways of fusing stem cells with injured or degenerated muscle

fibers.

Fusion between cell membranes plays a key role in development of

different kinds of bone cells, placental cells, and immune system

cells, as well as in fertilization and in the penetration of viruses

into living cells. Understanding how membrane fusion takes place may

one day lead to the development of ways to encourage the process

when it's needed or hinder it when it's likely to cause harm.

Prof. Ben-Zion Shilo's research is supported by the M. D. Moross

Institute for Cancer Research; the Y. Leon Benoziyo Institute for

Molecular Medicine; the Clore Center for Biological Physics; the Dr.

f Cohn Minerva Center for Biomembrane Research; the J & R Center

for Scientific Research; and the Jeanne and ph Nissim Foundation

for Life Sciences Research. Prof. Shilo is the incumbent of the

Hilda and Cecil Professorial Chair in Molecular Genetics.