The Eyes Have It: A Step Toward Creating Peepers in a Petri Dish
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- Date: Wed, 24 Oct 2007 21:04:06 -0400
Scientific American
Wednesday, October 24, 2007
The Eyes Have It: A Step Toward Creating Peepers in a Petri Dish
By Nikhil Swaminathan
Study fingers a enzyme that jump starts the pathway leading to the generation
of eye tissues
Quote: "This work may have interesting implications for the stem cell field"
COMING TO A LAB NEAR YOU: Researchers identify an enzyme that starts a cascade
of cellular events involved in the development of eyes.
An accidental discovery could pave the way to one day coaxing stem cells to
develop into human eyes in the lab.
A team of scientists at the University of Warwick in England studying the
development of motility in frogs found that a certain ectoenzyme (a
cell-surface protein) injected into a tadpole embryo triggered the development
of tissues that eventually form eyes.
Further experimentation led the researchers to conclude that the surface
protein is, in fact, an early player in the cellular cascade that leads to eye
formation. Researchers say the finding could be harnessed in the future to make
an "eye in a dish," a tool that would be invaluable in coaxing stem cells to
develop into ocular tissues.
"Our study provides clear discovery of upstream signals controlling a
previously known pathway controlling eye development and therefore provides a
step closer to being able to manipulate eye development," explains Elizabeth A.
Jones, a professor in the university's biological sciences department and a
co-author of the study published in Nature.
Ectonucleoside triphosphate diphosphohydrolase 2 (E-NTPDase2) is an ectoenzyme
that, along with family members E-NTPDase1 and E-NTPDase3, is known to degrade
the chemical compound ATP (adenosine triphosphate) into ADP (adenosine
diphosphate) for the purpose of sending messages to cells to change the fleet
of proteins they are producing. Primarily, ATP functions as the energy currency
of cells but, in some varieties, a tiny amount is secreted into the space
between cells, where it latches onto a neighbor to induce particular responses
and modulations. Both ATP and ADP, known as purines, can transmit signals to
cells that change their developmental activity. The research team found that
when it increased levels of E-NTPDase2 in tadpole embryos that consisted of
only eight cells, they could cause parts of the eye to form not only on the
heads of the amphibians, but also in tissues in other parts of their bodies,
including their tails. Minute pulses of ATP are released into extra
cellular areas mostly by cells in the head where the eyes are supposed to
develop. Jones notes that at temporally distinct moments, other cells in the
body may expel small packets of ATP, which in the presence of E-NTPDase2 can
cause eye tissue to form.
Through many rounds of analysis, both by amplifying and decreasing the levels
of certain chemicals as well as knocking out the function of certain genes that
code for proteins that regulate eye development (called eye field transcription
factors), the scientists determined that E-NTPDase2 (although not E-NTPDase 1
or 3) was the only ectoenzyme that could drive eye development. Further, they
determined that it must act early in the pathway that leads to the formation of
the eye. After it converts ATP to ADP, the level of the latter accumulates
outside the cell and the purine can bind to a purine receptor called P2Y1.
"It is the activation of this receptor that either directly or indirectly turns
on the expression of the eye-field transcription factors," Jones says. "We
don?t quite know the mechanisms involved between going from the receptor and
turning on the genes, and this is an area for future investigation."
Jones and her colleagues believe that most of the eye development pathway is
conserved between frogs and humans. Damage to human chromosome 9 (of the cell's
24 pairs) where the gene that codes for E-NTPDase2 resides is known to cause
eye and brain defects, such as microphthalmia-literally, small eyes. This means
that down the road, researchers might be able to create an "eye in a dish."
"This work may have interesting implications for the stem cell field," says
Richard Lang, a professor of developmental biology at the Cincinnati Children's
Hospital Research Foundation. "The activity of purine signaling in inducing eye
field precursors," he says, "might be a very useful tool for the culture
dish-generation of progenitor cells for a variety of eye cell types."
http://www.sciam.com/article.cfm?chanID=sa003&articleID=D42A2914-E7F2-99DF-3F786D77E85431C6&ref=rdf
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