Genomic Analysis of Mouse Retinal Development

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.

New meaning in the message: Noncoding RNAs and their role in retinal development

“…By contrast, pri-miR-124a-1 (previously reported as RNCR3) represents over 0.2% of total polyadenylated transcripts in the postnatal retina, making it more abundant than beta-actin mRNA (Blackshaw et al, 2004). Examination of public SAGE data indicates that this pri-miRNA is equally abundant in the human retina.…”

“…Examination of public SAGE data indicates that this pri-miRNA is equally abundant in the human retina. Analysis of SAGE data also indicates that the pri forms of miR-124a-2 and miR-9 are abundant in both human and mouse retinas, though less so than pri-miR124a-1 (Sharon et al, 2002;Blackshaw et al, 2004). By contrast, the pri-form of the highly retinal-enriched miR-96/182/ 183 cluster is barely detectable even by RT-PCR, so abundance of some primiRNAs is unlikely to reflect general deficiencies in miRNA processing in retina .…”

“…While large-scale efforts at gene expression profiling in retinal progenitors (Blackshaw et al, 2004;Livesey et al, 2004) have identified a considerable diversity of gene expression patterns among progenitors, very few genes show coordinated, temporally restricted expression across large subsets of progenitors, as would be predicted from the competence model. This suggests that changes in mRNA levels of effector genes may not be sufficient to drive changes in developmental competence.…”

“…The first OST identified that corresponded to a protein-coding gene that plays an important role in retinal development was the Six3-associated OST, initially termed RNCR1 (Blackshaw et al, 2004). Analysis of SAGE tags for Six3 and RNCR1 revealed that these two transcripts showed an almost identical temporal expression pattern, with expression of both RNAs high in retinal progenitors and decreasing dramatically with the end of retinal neurogenesis.…”

“…Six3OS is essentially coexpressed with Six3 in retinal and diencephalic progenitor cells, while several other regions of the developing brain that express Six3 do not express Six3OS (Geng et al, 2007). In the mature retina, different Six3OS splice forms show differing expression, with some isoforms coexpressed with Six3 in retinal ganglion cells while others are restricted to Muller glia, which do not express Six3 (Blackshaw et al, 2004;Geng et al, 2007). Other HOSTs are expressed in very different cellular patterns from their partnered homeodomain transcription factors.…”