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Making eyes
For a fly eye to develop, a protein called spalt must turn on, then off, then on again
By KRISTINE KELLY
Timing, as the saying goes, is everything.
By manipulating the timing of gene expression,
Rockefeller researchers led by assistant professor Bertrand
Mollereau, in the Strang Laboratory of Cancer Research, were able
to change the development and function of cells in the fly eye
— in one instance even causing the flies to become
colorblind.
Like the common housefly, fruit flies have
compound eyes, each of which contains about 800 light-sensitive
clusters known as ommatidia. Each ommatidial cluster has eight
photoreceptor cells, designated R1 through R8. The first six
photoreceptors form an outer circle, and they detect motion and
enable the flies to see in dim light. The inner two, R7 and R8, are
required for color vision.
In previous research completed while he was a
postdoctoral fellow at New York University, Mollereau discovered a
protein that regulates gene expression — the transcription
factor spalt — that controls the fly’s ability to see
color. By breeding flies that lacked spalt, the mutant flies
developed eyes missing the R7 and R8 cells, rendering the flies
colorblind. But two studies, done at Rockefeller, show that for the
ommatidia to develop correctly, spalt must be present in several of
the photoreceptor cells.
“Before spalt is used to establish the
color vision cells R7 and R8, it is first needed for the proper
development of two other photoreceptor cells — R3 and
R4,” says Pedro Domingos, a postdoc in Hermann Steller’s
lab who worked on the research. “However, it needs to be
expressed at the right time in each of the cells; the spalt gene is
actually turned on, and then turned off, several times during
development.
“What this research shows is that
depending on the timing, the same signal can be used over and over
again to generate different cell specializations within the fly
eye,” says Domingos.
Beyond detecting motion, the R3 and R4 cells
also help arrange the ommatidia into their final design: a spoked,
circular pattern similar to a daisy flower. “The cells of the
ommatidia need to rotate into position during development,”
Mollereau says. “The direction they rotate in is controlled
by the R3 and R4 cells and is very specific.” If the spalt
protein isn’t made, the ommatidia have no organization.
Normally, expression of spalt is fading in the
R3 and R4 cells just as it is beginning to increase in the R7 color
vision cells. Surprisingly, when the team artificially maintained
spalt expression longer than normal during R3 and R4 development
they were transformed into color vision cells. The scientists were
able to change the fate and function of the cells just by controlling the timing of
spalt gene expression. For R3 and R4 cells to form, the scientists
realized that another protein must be capable of turning spalt off.
Mollereau and colleagues found that the
protein responsible for shutting off spalt is called seven-up, a
protein that has not been previously linked to spalt. “In the
R3 cell, spalt actually induces seven-up expression after a while.
Then seven-up represses spalt to keep the cells from turning into
an R7,” Mollereau says. “It’s like a dog biting
his own tail.”
Mollereau’s research, reported in the
September 2004 issue of Developmental
Biologyand the November 2004 issue of Development, may
eventually help scientists understand the mechanisms behind retinal
degeneration and other sight disorders. More immediately, it may
have implications for Townes-Brocks’ syndrome, which has
already been linked to spalt and results in hearing loss and limb
deformities.
August 26, 2005
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