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NSF PR 99-11 - February 18, 1999
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Molecular Control Mechanism Of Embryonic Development
Unraveled
National Science Foundation (NSF)-funded researchers
at the Johns Hopkins School of Medicine in Baltimore,
Maryland, and at California's Stanford University
have shed new light on the molecular switches that
control the complex process by which a single fertilized
egg develops into a mature organism. Their paper is
published in the February 19, 1999, issue of the journal
Cell.
In humans and other mammals, the process is orchestrated
in the developing embryo by a set of proteins called
"Hox proteins" that control the timely expression
of genes -- and thereby control the production of
the "next stage" proteins needed for embryonic development.
The action of Hox proteins must, in turn, be coordinated
to assure the accurate development of an embryo; that
coordination involves another set of proteins that
act as molecular choreographers.
"Failure of the molecular systems that control development
prevents normal embryonic growth, and alterations
in these control systems can lead to a wide variety
of cancers," explains Kamal Shukla, program director
in NSF's division of cellular and molecular biosciences,
which funds the research. "Understanding the molecular
mechanisms that control normal embryonic development
is the first step in developing strategies to prevent
these errors, or to repair them when they have gone
wrong." Cynthia Wolberger at Johns Hopkins and Michael
Cleary at Stanford have made a major step forward
in the understanding of these crucial molecular events,
Shukla believes.
This research, which uses x-ray crystallography, has
led to the determination of the atomic structure of
"HoxB1" and a protein called Pbx1, all bound to a
fragment of DNA. Pbx1 plays a central role in the
modulation of Hox protein function, and mutations
in it have been implicated in some childhood leukemias.
By visualizing how Pbx1 interacts with a Hox protein
and with DNA, Wolberger and colleagues have determined
the precise way in which the proteins interact with
one another to control development.
Pbx1, by interacting with Hox proteins, is able to
control the expression of many different types of
proteins, says Wolberger. "Understanding how they
interact with partner proteins such as Pbx1 and with
DNA is key to knowledge of the mechanism by which
a developing organism grows from a single fertilized
egg cell into a fully differentiated creature with
head and tail, arms and legs."
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