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July 23, 2002
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Researchers Identify Eye-Formation Strategy in Mice
at the University of California, San Diego (UCSD) School of Medicine have
discovered a linkage between proteins that is an essential part of the
complex series of molecular events leading to normal eye development in
mice. The investigators also suggest that the combination of specific
proteins in eye formation may be similar to yet unidentified genes that
act together to allow development of other organs.
in the July 19, 2002 issue of the journal Science, the research was done
in the lab of Michael G. Rosenfeld, Ph.D., UCSD professor of medicine
and an investigator with the Howard Hughes Medical Institute. The
first author was Xue Li, Ph.D., a post-doctoral fellow in the Rosenfeld
central issue in development of any mammalian organ is to get the right
number of cells which make the size of each organ precise." Rosenfeld
studies with embryonic mice, the research team found that sine oculis/6
(Six6), one of a family of genes naturally expressed in eye development,
actively enable normal eye size by stopping another set of genes that
restrict eye cell-growth if left alone.
Mice bred without the Six6 protein exhibited arrested eye development,
sometimes with complete absence of optic nerve and optic chiasm, the location
of x-crossed nerve fibers on the undersurface of the hypothalamus.
determine if Six6 had a co-factor, or accomplice, in its developmental
role, the researchers investigated it and other genes in cell cultures.
They found that Six6 strongly interacted with another protein called dachshund/2
(Dach2). While Six6 alone exerted a weak repressive activity, it strongly
assumed its normal role when associated with Dach2.
research team also discovered that the linked Six6/Dach2 complex interacted
with a gene called p27Kip1, a known inhibitor of cell proliferation. In
cell cultures, they identified the region of the p27Kip1 gene where the
Six6/Dach2 complex bound, then studied mouse retinas to prove that Six6/Dach2
regulated p27Kip1 acted together to control tissue growth.
authors note in the paper that "together, these findings provide
an organ-specific strategy for the expansion of precursor cell populations
during development, a strategy likely to be used in other organ systems."
Rosenfeld lab work was supported by grants from the National Institutes
of Health, NRSA and Telethon/Italy.
In addition to Rosenfeld and Li, authors of the paper are Valentina Perissi, a UCSD graduate student, David W. Rose, Ph.D., UCSD associate professor of medicine, and Forrest Liu, M.D., UCSD Department of Medicine.
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