http://unisci.com/stories/20013/0831016.htm
31-Aug-2001
The difference between a group of
"blank" stem cells and a developing fetus is a complex series of biochemical
reactions that transform stem cells into specific types of body tissue.
In this week's issue of Science,
researchers at the University of Pennsylvania Medical Center report how
the enzyme QSulf1 fits into this biochemical clockwork, helping cells respond
to one of the many chemical signals that surround them.
"It is a problem at the heart of
basic biology -- how one cell becomes muscle while an adjacent cell turns
to bone," said Charles P. Emerson, PhD, Joseph P. Leidy Professor of Biology
and Chair of Penn's Department of Cell and Developmental Biology. "For
all we know of stem cells and the molecules involved in cell differentiation,
we know very little about how these processes physically work."
As an embryo develops, different
molecular signals instruct cells to produce proteins that will transform
the cell into a particular tissue type, such as bone or muscle. QSulf1
functions in progenitor cells, slightly more advanced forms of stem cells
that have fewer potential career paths.
According to the researchers, QSulf1
represents a new class of enzymes whose main function is to modify an important
signaling co-factor called heparan sulfate proteoglycan (HSPG). It is a
small yet important step in a chain of reactions involved in allowing a
cell to respond to a specific molecular signal, Wnt, and transforming the
cell into muscle instead of skin or bone.
"It is not enough to know what proteins
are involved in embryonic development, we must understand how they work
in order to eventually understand how to fix them when they fail," said
Emerson.
Based on their findings, the researchers
propose that Qsulf1 is released
As a result, Wnt signaling molecules,
which are bound to HSPGs on the surfaces of cells, are released, allowing
Wnts to activate regulatory genes that give further career instructions.
In this study, the researchers show
that QSulf1 allows embryonic cells to express a muscle master regulatory
gene called MyoD, which then instructs these cells to become muscle progenitor
cells instead of skin or bone progenitor cells.
These findings are not only of interest
to researchers in the fields of cell biology and developmental diseases,
but also highlight how much remains to be learned about the complex workings
of the developing embryo.
Emerson and his colleagues first
identified QSulf1 as they studied bird embryos for genes whose expression
is controlled by Shh, a molecule of known importance in developmental processes.
Interestingly, the QSulf1 gene remains essentially unchanged within the
genomes of worms, flies, mice and humans.
"Evolution has seen fit to keep this
protein around a long time," said Emerson. "What we see is the emerging
picture of a fundamental player in the embryonic development of many types
of organisms."
Understanding the mechanisms of stem
cell specification will unlock potential new technologies for the repair
of organs and tissues damaged by disease and trauma.
"If we are going to use stem cells
to treat developmental disorders, there is still a great deal that basic
biology must tell us," said Emerson. "We are only now beginning to understand
how the body builds tissues."
Other Penn scientists who participated
in the study are Marcus K. Gustafsson; Weitao Sun; Xingbin Ai, PhD, and
David M. Standiford, PhD. Gurtej K. Dhoot, PhD, of the Royal Veterinary
College, University of London, also collaborated in the research.
The research was funded by the National
Institutes of Health and the Royal Society and Wellcome Trust. -
Copyright © 1995-2001 UniSci
By Greg Lester
[Contact: Ellen O'Brien]
onto the surface of specific embryonic
cells where it snips off a specific sulfur-containing chemical group (called
a sulfate group) that projects from a specific part of the HSPG molecule.