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doi: 10.1242/10.1242/dev.00114
Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA
* Author for correspondence (e-mail: cepko{at}genetics.med.harvard.edu)
Accepted 22 August 2002
The paired type homeodomain gene, Rax, was previously identified
as a key molecule in early eye formation in mice and humans. We report the
expression patterns of two Rax family members from chicken, Rax and
RaxL, and on the function of RaxL in photoreceptor
development. Both Rax and RaxL are expressed in early
retinal progenitor cells, with Rax being expressed at a significantly
higher level than RaxL. At the time that photoreceptors begin to
form, RaxL appears at a relatively high level in a subset of cells
within the zone of proliferating progenitor cells. Subsequently, it is
expressed in cells migrating to the photoreceptor layer, where it is highly
expressed during the initial, but not late, stages of photoreceptor
differentiation. To test the function of RaxL, a putative
dominant-negative allele of RaxL comprising a fusion of the
engrailed repressor domain and a region of RaxL
(EnRaxL
C) was introduced in vivo into the early chick eye using a
retroviral vector. EnRaxLC, but not the dominant negative Rax
(EnRaxC), caused a significant reduction in expression of early markers
of photoreceptor cells. Examination of the transactivation activity of RaxL on
a reporter construct bearing a canonical photoreceptor-specific enhancer
element showed that RaxL exhibited significant activation activity, and that
this activity was severely diminished in the presence of EnRaxLC. The
effect on photoreceptor gene expression in vivo was specific in that other
cell types were unaffected, as was general proliferation in the retina. The
reduction in numbers of cells expressing photoreceptor markers was probably
due to decreased survival of developing photoreceptor cells, as there was
increased apoptosis among cells of the retina expressing dominant-negative
RaxL. We propose that RaxL plays a role in the initiation of
differentiation, and also possibly commitment, of photoreceptor cells in the
chicken retina.
Key words: Photoreceptors, Rx, Rax, RaxL, Retina, Homeodomain protein, Cell fate, Cell differentiation, Chicken
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