XB-ART-34399
Invest Ophthalmol Vis Sci
October 1, 2006;
47
(10):
4245-53.
The Rx-like homeobox gene (Rx-L) is necessary for normal photoreceptor development.
Abstract
The retinal homeobox (Rx) gene plays an essential role in retinal development. An Rx-like (
Rx-L) gene from Xenopus laevis has been identified. The purpose of this study was to analyze the function of
Rx-L in the developing
retina. DNA-binding properties of
Rx-L were analyzed by electrophoretic mobility shift assay (EMSA), with in vitro-translated proteins and radiolabeled oligonucleotide probe. The
Rx-L expression pattern was analyzed by in situ hybridization using whole or sectioned embryos and digoxigenin-labeled antisense riboprobes.
Rx-L loss of function was studied by using antisense morpholino oligonucleotides targeted to the
Rx-L translation initiation site. Embryos injected with control or
Rx-L morpholinos were analyzed at
stage 41 or 45.
Rx-L shares homology with Rx at the homeo-, OAR, and Rx domains, but lacks an octapeptide motif.
Rx-L is expressed in the developing
retina beginning in the
early tailbud stage. In the maturing
retina,
Rx-L expression is restricted primarily to the developing
photoreceptor layer and the
ciliary marginal zone.
Rx-L can bind a photoreceptor conserved element-1 (
PCE-1) oligonucleotide, an element conserved among all known photoreceptor gene promoters. In a promoter activity assay,
Rx-L functions as a stronger transcriptional activator than Rx. Antisense morpholino-mediated knockdown of
Rx-L expression resulted in a decrease in
rhodopsin and
red cone opsin expression levels in Xenopus retinas. Injection of the
Rx-L antisense morpholino oligonucleotide also resulted in a decrease in the length of both rod and cone outer segments. The results suggest that
Rx-L functions to regulate rod and cone development by activating photoreceptor-specific gene expression.
PubMed ID:
17003412
PMC ID:
PMC2824340
Article link:
Invest Ophthalmol Vis Sci
Grant support:
[+]
Species referenced:
Xenopus
Genes referenced:
ces3.7
opn1lw
rax2
rho
Antibodies:
Isl1/2 Ab1
Morpholinos:
rax2 MO1
References [+] :
Andreazzoli,
Role of Xrx1 in Xenopus eye and anterior brain development.
1999,
Pubmed,
Xenbase
Andreazzoli,
Role of Xrx1 in Xenopus eye and anterior brain development.
1999,
Pubmed
,
Xenbase
Bailey,
Regulation of vertebrate eye development by Rx genes.
2004,
Pubmed
,
Xenbase
Batni,
Characterization of the Xenopus rhodopsin gene.
1996,
Pubmed
,
Xenbase
Casarosa,
Xrx1, a novel Xenopus homeobox gene expressed during eye and pineal gland development.
1997,
Pubmed
,
Xenbase
Chang,
Sequential genesis and determination of cone and rod photoreceptors in Xenopus.
1998,
Pubmed
,
Xenbase
Chen,
Groucho/TLE family proteins and transcriptional repression.
2000,
Pubmed
Chen,
The chicken RaxL gene plays a role in the initiation of photoreceptor differentiation.
2002,
Pubmed
Chen,
Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes.
1997,
Pubmed
Chow,
Early eye development in vertebrates.
2001,
Pubmed
Chuang,
Zebrafish genes rx1 and rx2 help define the region of forebrain that gives rise to retina.
2001,
Pubmed
Chuang,
Expression of three Rx homeobox genes in embryonic and adult zebrafish.
1999,
Pubmed
Dasen,
Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis.
2001,
Pubmed
El-Hodiri,
xnf7 functions in dorsal-ventral patterning of the Xenopus embryo.
1997,
Pubmed
,
Xenbase
Fisher,
Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates.
1998,
Pubmed
,
Xenbase
Furukawa,
rax, a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina.
1997,
Pubmed
Galliot,
Evolution of homeobox genes: Q50 Paired-like genes founded the Paired class.
1999,
Pubmed
Johnson,
Interphotoreceptor matrix domains ensheath vertebrate cone photoreceptor cells.
1986,
Pubmed
Kim,
Isolation and characterization of XKaiso, a transcriptional repressor that associates with the catenin Xp120(ctn) in Xenopus laevis.
2002,
Pubmed
,
Xenbase
Kimura,
Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression.
2000,
Pubmed
Krieg,
In vitro RNA synthesis with SP6 RNA polymerase.
1988,
Pubmed
Li,
A single morphogenetic field gives rise to two retina primordia under the influence of the prechordal plate.
1997,
Pubmed
,
Xenbase
Loosli,
Medaka eyeless is the key factor linking retinal determination and eye growth.
2001,
Pubmed
Loosli,
Loss of eyes in zebrafish caused by mutation of chokh/rx3.
2003,
Pubmed
Ma,
Retina-specific cis-elements and binding nuclear proteins of carp rhodopsin gene.
2001,
Pubmed
Mani,
Xenopus rhodopsin promoter. Identification of immediate upstream sequences necessary for high level, rod-specific transcription.
2001,
Pubmed
,
Xenbase
Marquardt,
Transcriptional control of neuronal diversification in the retina.
2003,
Pubmed
Marquardt,
Generating neuronal diversity in the retina: one for nearly all.
2002,
Pubmed
Mathers,
The Rx homeobox gene is essential for vertebrate eye development.
1997,
Pubmed
,
Xenbase
Meijlink,
Vertebrate aristaless-related genes.
2000,
Pubmed
Mitton,
The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation.
2000,
Pubmed
Molenaar,
Differential expression of the Groucho-related genes 4 and 5 during early development of Xenopus laevis.
2000,
Pubmed
,
Xenbase
Moritz,
Xenopus laevis red cone opsin and Prph2 promoters allow transgene expression in amphibian cones, or both rods and cones.
2002,
Pubmed
,
Xenbase
Ohuchi,
Identification of chick rax/rx genes with overlapping patterns of expression during early eye and brain development.
1999,
Pubmed
,
Xenbase
Perron,
Retinal stem cells in vertebrates.
2000,
Pubmed
Rehemtulla,
The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression.
1996,
Pubmed
Rubenstein,
Localizing the adhesive and signaling functions of plakoglobin.
1997,
Pubmed
,
Xenbase
Su,
Structural characterization and transcriptional pattern of two types of carp rhodopsin gene.
2000,
Pubmed
Tucker,
The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene.
2001,
Pubmed
,
Xenbase
Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase
Uehara,
Localization of fluorescence-labeled lectin binding sites on photoreceptor cells of the monkey retina.
1983,
Pubmed
Viczian,
XOtx5b and XOtx2 regulate photoreceptor and bipolar fates in the Xenopus retina.
2003,
Pubmed
,
Xenbase
Voronina,
Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea.
2004,
Pubmed
Wang,
QRX, a novel homeobox gene, modulates photoreceptor gene expression.
2004,
Pubmed
Wawersik,
Vertebrate eye development as modeled in Drosophila.
2000,
Pubmed
Whitaker,
Conserved transcriptional activators of the Xenopus rhodopsin gene.
2004,
Pubmed
,
Xenbase
Zaghloul,
Step-wise specification of retinal stem cells during normal embryogenesis.
2005,
Pubmed
Zuber,
Specification of the vertebrate eye by a network of eye field transcription factors.
2003,
Pubmed
,
Xenbase