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Genomic analysis of mouse retinal development.

Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, Weber G, Lee K, Fraioli RE, Cho SH, Yung R, Asch E, Ohno-Machado L, Wong WH, Cepko CL - PLoS Biol. (2004)

Bottom Line: The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions.In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs") were found to be dynamically and specifically expressed in developing and mature retinal cell types.These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
The vertebrate retina is comprised of seven major cell types that are generated in overlapping but well-defined intervals. To identify genes that might regulate retinal development, gene expression in the developing retina was profiled at multiple time points using serial analysis of gene expression (SAGE). The expression patterns of 1,051 genes that showed developmentally dynamic expression by SAGE were investigated using in situ hybridization. A molecular atlas of gene expression in the developing and mature retina was thereby constructed, along with a taxonomic classification of developmental gene expression patterns. Genes were identified that label both temporal and spatial subsets of mitotic progenitor cells. For each developing and mature major retinal cell type, genes selectively expressed in that cell type were identified. The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions. In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs") were found to be dynamically and specifically expressed in developing and mature retinal cell types. Finally, many photoreceptor-enriched genes that mapped to chromosomal intervals containing retinal disease genes were identified. These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

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Catalog of Gene Expression in Adult RetinaThe most commonly observed patterns of gene expression in the adult retina are indicated. Data are taken from Table S5 and cover all genes examined in the adult retina. Genes are placed in a category corresponding to a single cell type if expression is substantially greater in that cell type than in any of the other cell types examined. Genes are placed in categories corresponding to multiple cell types if expression is approximately equal in more than one cell type. The number of genes expressed in photoreceptors and Müller glia differs somewhat from those used in the analysis shown in Figure 5A, since the expression of a large number of photoreceptor-enriched genes was not examined prenatally, and a number of Müller-enriched genes were detectable in Müller glia through the end of the second postnatal week, but not in adult retina. AC, amacrine cells; BC, bipolar cells; GC,ganglion cells; HC, horizontal cells; MG, Müller glia; sAC, subset of amacrine cells; sBC, subset of bipolar cells; sGC, subset of ganglion cells
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pbio-0020247-g007: Catalog of Gene Expression in Adult RetinaThe most commonly observed patterns of gene expression in the adult retina are indicated. Data are taken from Table S5 and cover all genes examined in the adult retina. Genes are placed in a category corresponding to a single cell type if expression is substantially greater in that cell type than in any of the other cell types examined. Genes are placed in categories corresponding to multiple cell types if expression is approximately equal in more than one cell type. The number of genes expressed in photoreceptors and Müller glia differs somewhat from those used in the analysis shown in Figure 5A, since the expression of a large number of photoreceptor-enriched genes was not examined prenatally, and a number of Müller-enriched genes were detectable in Müller glia through the end of the second postnatal week, but not in adult retina. AC, amacrine cells; BC, bipolar cells; GC,ganglion cells; HC, horizontal cells; MG, Müller glia; sAC, subset of amacrine cells; sBC, subset of bipolar cells; sGC, subset of ganglion cells

Mentions: A molecular catalog of gene expression in the adult retina was assembled with molecular markers for every major class of retinal cell (Figure 7). The catalog of photoreceptor-enriched genes reported in previous work (Blackshaw et al. 2001) was expanded, and a large number of genes expressed in the inner retina were identified. Some of these include genes that mark subsets of amacrine and ganglion cells. Knowledge of which genes show cell-specific expression in the retina can aid in identifying retinal disease genes. The expression of nearly half of all cloned photoreceptor dystrophy genes is selectively enriched in photoreceptors (Blackshaw et al. 2001), while hereditary optic neuropathies have been suggested to be partially mediated by mutations in ganglion-cell-enriched genes (Votruba et al. 1998). Furthermore, a number of other retinal and anterior segment abnormalities result from mutations in genes that are broadly expressed in retinal progenitor cells (Hanson et al. 1999; Ferda Percin et al. 2000). See Table S13 for a full list of the chromosomal locations of the human orthologs of genes examined in this work. This list also contains a full list of mapped but unidentified Mendelian human retinal disease genes and orthologs of photoreceptor-enriched genes identified in this work that lie within those chromosomal intervals. A total of 164 photoreceptor-enriched genes not previously linked to retinal disease were found in chromosomal intervals containing retinal disease loci, representing a total of 42 distinct loci. While photoreceptor-enriched transcripts make up roughly half of all cloned retinal disease genes (Blackshaw et al. 2001), roughly one-third of retinal disease genes are expressed in all cells of the retina, suggesting that it is fruitful to consider such genes when screening candidate disease genes. We find that 22 panretinally expressed genes map within intervals containing unidentified disease genes, representing 16 distinct loci.


Genomic analysis of mouse retinal development.

Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, Weber G, Lee K, Fraioli RE, Cho SH, Yung R, Asch E, Ohno-Machado L, Wong WH, Cepko CL - PLoS Biol. (2004)

Catalog of Gene Expression in Adult RetinaThe most commonly observed patterns of gene expression in the adult retina are indicated. Data are taken from Table S5 and cover all genes examined in the adult retina. Genes are placed in a category corresponding to a single cell type if expression is substantially greater in that cell type than in any of the other cell types examined. Genes are placed in categories corresponding to multiple cell types if expression is approximately equal in more than one cell type. The number of genes expressed in photoreceptors and Müller glia differs somewhat from those used in the analysis shown in Figure 5A, since the expression of a large number of photoreceptor-enriched genes was not examined prenatally, and a number of Müller-enriched genes were detectable in Müller glia through the end of the second postnatal week, but not in adult retina. AC, amacrine cells; BC, bipolar cells; GC,ganglion cells; HC, horizontal cells; MG, Müller glia; sAC, subset of amacrine cells; sBC, subset of bipolar cells; sGC, subset of ganglion cells
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC439783&req=5

pbio-0020247-g007: Catalog of Gene Expression in Adult RetinaThe most commonly observed patterns of gene expression in the adult retina are indicated. Data are taken from Table S5 and cover all genes examined in the adult retina. Genes are placed in a category corresponding to a single cell type if expression is substantially greater in that cell type than in any of the other cell types examined. Genes are placed in categories corresponding to multiple cell types if expression is approximately equal in more than one cell type. The number of genes expressed in photoreceptors and Müller glia differs somewhat from those used in the analysis shown in Figure 5A, since the expression of a large number of photoreceptor-enriched genes was not examined prenatally, and a number of Müller-enriched genes were detectable in Müller glia through the end of the second postnatal week, but not in adult retina. AC, amacrine cells; BC, bipolar cells; GC,ganglion cells; HC, horizontal cells; MG, Müller glia; sAC, subset of amacrine cells; sBC, subset of bipolar cells; sGC, subset of ganglion cells
Mentions: A molecular catalog of gene expression in the adult retina was assembled with molecular markers for every major class of retinal cell (Figure 7). The catalog of photoreceptor-enriched genes reported in previous work (Blackshaw et al. 2001) was expanded, and a large number of genes expressed in the inner retina were identified. Some of these include genes that mark subsets of amacrine and ganglion cells. Knowledge of which genes show cell-specific expression in the retina can aid in identifying retinal disease genes. The expression of nearly half of all cloned photoreceptor dystrophy genes is selectively enriched in photoreceptors (Blackshaw et al. 2001), while hereditary optic neuropathies have been suggested to be partially mediated by mutations in ganglion-cell-enriched genes (Votruba et al. 1998). Furthermore, a number of other retinal and anterior segment abnormalities result from mutations in genes that are broadly expressed in retinal progenitor cells (Hanson et al. 1999; Ferda Percin et al. 2000). See Table S13 for a full list of the chromosomal locations of the human orthologs of genes examined in this work. This list also contains a full list of mapped but unidentified Mendelian human retinal disease genes and orthologs of photoreceptor-enriched genes identified in this work that lie within those chromosomal intervals. A total of 164 photoreceptor-enriched genes not previously linked to retinal disease were found in chromosomal intervals containing retinal disease loci, representing a total of 42 distinct loci. While photoreceptor-enriched transcripts make up roughly half of all cloned retinal disease genes (Blackshaw et al. 2001), roughly one-third of retinal disease genes are expressed in all cells of the retina, suggesting that it is fruitful to consider such genes when screening candidate disease genes. We find that 22 panretinally expressed genes map within intervals containing unidentified disease genes, representing 16 distinct loci.

Bottom Line: The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions.In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs") were found to be dynamically and specifically expressed in developing and mature retinal cell types.These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
The vertebrate retina is comprised of seven major cell types that are generated in overlapping but well-defined intervals. To identify genes that might regulate retinal development, gene expression in the developing retina was profiled at multiple time points using serial analysis of gene expression (SAGE). The expression patterns of 1,051 genes that showed developmentally dynamic expression by SAGE were investigated using in situ hybridization. A molecular atlas of gene expression in the developing and mature retina was thereby constructed, along with a taxonomic classification of developmental gene expression patterns. Genes were identified that label both temporal and spatial subsets of mitotic progenitor cells. For each developing and mature major retinal cell type, genes selectively expressed in that cell type were identified. The gene expression profiles of retinal Müller glia and mitotic progenitor cells were found to be highly similar, suggesting that Müller glia might serve to produce multiple retinal cell types under the right conditions. In addition, multiple transcripts that were evolutionarily conserved that did not appear to encode open reading frames of more than 100 amino acids in length ("noncoding RNAs") were found to be dynamically and specifically expressed in developing and mature retinal cell types. Finally, many photoreceptor-enriched genes that mapped to chromosomal intervals containing retinal disease genes were identified. These data serve as a starting point for functional investigations of the roles of these genes in retinal development and physiology.

Show MeSH
Related in: MedlinePlus