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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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Müller-Glia-Enriched Genes(A) Müller-glia-enriched genes show stronger expression in retinal progenitors than do genes enriched in other postnatally born cell types. See Materials and Methods for details of how progenitor-enriched and cell-specific expression patterns were determined, and p-values for progenitor-enrichment of genes that are cell type–specific in the mature retina were calculated. Data on 4N-enriched transcripts were obtained from Livesey et al. (2004). Numbers for each value are as follows. For N, the number of cell-enriched genes, NMG = 86, NPr = 112, NBC = 21, and NAC = 57. For I, the number of genes that show retinal progenitor-enriched patterns by ISH, Itotal = 180, IMG = 66, IPR = 15, IBC = 4, and IAC = 8. For M, the number of genes enriched in 4N retinal progenitor cells that were tested by ISH in adult retina, Mtotal = 28, MMG = 12, MPR = 3, MBC = 3, and MAC = 1. *, p < 10−13; **, p < 0.0001.(B) Müller-glia-enriched genes show strong expression in mitotic progenitors. The genes shown are: Mm.26062/ADO24, Mm.55143/Dkk3, Mm.5021/DDR1, Mm.35817, Mm.20465/GPCR37, Mm.200608/clusterin, and Mm.22288/cyclin D1. Sections were from central retina. Cellular laminae of both the developing and mature retina are indicated with colored bars. All pictures were taken at 200x. See Table S5 for a full list of probes used.(C) Dynamic expression of metabolic genes in developing retina. Metabolic enzymes are often selectively expressed in mitotic progenitors and developing Müller glia. The genes shown are Mm.27953/glycine decarboxylase, Mm.9114/mu-crystallin, and Mm.213213/HK-R. Cellular laminae of both the developing and mature retina are indicated with colored bars. Sections were from central retina. All pictures were taken at 200x. See Table S5 for a full list of probes used.
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pbio-0020247-g005: Müller-Glia-Enriched Genes(A) Müller-glia-enriched genes show stronger expression in retinal progenitors than do genes enriched in other postnatally born cell types. See Materials and Methods for details of how progenitor-enriched and cell-specific expression patterns were determined, and p-values for progenitor-enrichment of genes that are cell type–specific in the mature retina were calculated. Data on 4N-enriched transcripts were obtained from Livesey et al. (2004). Numbers for each value are as follows. For N, the number of cell-enriched genes, NMG = 86, NPr = 112, NBC = 21, and NAC = 57. For I, the number of genes that show retinal progenitor-enriched patterns by ISH, Itotal = 180, IMG = 66, IPR = 15, IBC = 4, and IAC = 8. For M, the number of genes enriched in 4N retinal progenitor cells that were tested by ISH in adult retina, Mtotal = 28, MMG = 12, MPR = 3, MBC = 3, and MAC = 1. *, p < 10−13; **, p < 0.0001.(B) Müller-glia-enriched genes show strong expression in mitotic progenitors. The genes shown are: Mm.26062/ADO24, Mm.55143/Dkk3, Mm.5021/DDR1, Mm.35817, Mm.20465/GPCR37, Mm.200608/clusterin, and Mm.22288/cyclin D1. Sections were from central retina. Cellular laminae of both the developing and mature retina are indicated with colored bars. All pictures were taken at 200x. See Table S5 for a full list of probes used.(C) Dynamic expression of metabolic genes in developing retina. Metabolic enzymes are often selectively expressed in mitotic progenitors and developing Müller glia. The genes shown are Mm.27953/glycine decarboxylase, Mm.9114/mu-crystallin, and Mm.213213/HK-R. Cellular laminae of both the developing and mature retina are indicated with colored bars. Sections were from central retina. All pictures were taken at 200x. See Table S5 for a full list of probes used.

Mentions: Genes selectively expressed in Müller glia share a number of defining features. Mitotic retinal progenitor cells and Müller glia showed a great degree of transcriptional overlap—far more so than other retinal cells that differentiate postnatally. Of the genes identified as being specifically expressed in Müller glia after the first postnatal week, 68% were found to be enriched in mitotic progenitor cells based on their ISH pattern, in contrast to only 14% of photoreceptor-specific genes (Figure 5A). Of the genes identified as enriched in 4N progenitor cells by micorarray analysis (Livesey et al. 2004) that were tested by ISH in adult retina, 43% were enriched in Müller glia, compared to 11% that were enriched in photoreceptors.


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)

Müller-Glia-Enriched Genes(A) Müller-glia-enriched genes show stronger expression in retinal progenitors than do genes enriched in other postnatally born cell types. See Materials and Methods for details of how progenitor-enriched and cell-specific expression patterns were determined, and p-values for progenitor-enrichment of genes that are cell type–specific in the mature retina were calculated. Data on 4N-enriched transcripts were obtained from Livesey et al. (2004). Numbers for each value are as follows. For N, the number of cell-enriched genes, NMG = 86, NPr = 112, NBC = 21, and NAC = 57. For I, the number of genes that show retinal progenitor-enriched patterns by ISH, Itotal = 180, IMG = 66, IPR = 15, IBC = 4, and IAC = 8. For M, the number of genes enriched in 4N retinal progenitor cells that were tested by ISH in adult retina, Mtotal = 28, MMG = 12, MPR = 3, MBC = 3, and MAC = 1. *, p < 10−13; **, p < 0.0001.(B) Müller-glia-enriched genes show strong expression in mitotic progenitors. The genes shown are: Mm.26062/ADO24, Mm.55143/Dkk3, Mm.5021/DDR1, Mm.35817, Mm.20465/GPCR37, Mm.200608/clusterin, and Mm.22288/cyclin D1. Sections were from central retina. Cellular laminae of both the developing and mature retina are indicated with colored bars. All pictures were taken at 200x. See Table S5 for a full list of probes used.(C) Dynamic expression of metabolic genes in developing retina. Metabolic enzymes are often selectively expressed in mitotic progenitors and developing Müller glia. The genes shown are Mm.27953/glycine decarboxylase, Mm.9114/mu-crystallin, and Mm.213213/HK-R. Cellular laminae of both the developing and mature retina are indicated with colored bars. Sections were from central retina. All pictures were taken at 200x. See Table S5 for a full list of probes used.
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Related In: Results  -  Collection

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

pbio-0020247-g005: Müller-Glia-Enriched Genes(A) Müller-glia-enriched genes show stronger expression in retinal progenitors than do genes enriched in other postnatally born cell types. See Materials and Methods for details of how progenitor-enriched and cell-specific expression patterns were determined, and p-values for progenitor-enrichment of genes that are cell type–specific in the mature retina were calculated. Data on 4N-enriched transcripts were obtained from Livesey et al. (2004). Numbers for each value are as follows. For N, the number of cell-enriched genes, NMG = 86, NPr = 112, NBC = 21, and NAC = 57. For I, the number of genes that show retinal progenitor-enriched patterns by ISH, Itotal = 180, IMG = 66, IPR = 15, IBC = 4, and IAC = 8. For M, the number of genes enriched in 4N retinal progenitor cells that were tested by ISH in adult retina, Mtotal = 28, MMG = 12, MPR = 3, MBC = 3, and MAC = 1. *, p < 10−13; **, p < 0.0001.(B) Müller-glia-enriched genes show strong expression in mitotic progenitors. The genes shown are: Mm.26062/ADO24, Mm.55143/Dkk3, Mm.5021/DDR1, Mm.35817, Mm.20465/GPCR37, Mm.200608/clusterin, and Mm.22288/cyclin D1. Sections were from central retina. Cellular laminae of both the developing and mature retina are indicated with colored bars. All pictures were taken at 200x. See Table S5 for a full list of probes used.(C) Dynamic expression of metabolic genes in developing retina. Metabolic enzymes are often selectively expressed in mitotic progenitors and developing Müller glia. The genes shown are Mm.27953/glycine decarboxylase, Mm.9114/mu-crystallin, and Mm.213213/HK-R. Cellular laminae of both the developing and mature retina are indicated with colored bars. Sections were from central retina. All pictures were taken at 200x. See Table S5 for a full list of probes used.
Mentions: Genes selectively expressed in Müller glia share a number of defining features. Mitotic retinal progenitor cells and Müller glia showed a great degree of transcriptional overlap—far more so than other retinal cells that differentiate postnatally. Of the genes identified as being specifically expressed in Müller glia after the first postnatal week, 68% were found to be enriched in mitotic progenitor cells based on their ISH pattern, in contrast to only 14% of photoreceptor-specific genes (Figure 5A). Of the genes identified as enriched in 4N progenitor cells by micorarray analysis (Livesey et al. 2004) that were tested by ISH in adult retina, 43% were enriched in Müller glia, compared to 11% that were enriched in photoreceptors.

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