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J. Jaszai, D. Corbeil; Identification and Distribution of Prominin-Like Molecules in the Retina of Lower Vertebrate Model Organisms. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4030.
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Mutations in the human PROM1 gene, encoding for the pentaspan transmembrane glycoprotein prominin-1, have been previously linked with autosomal recessive progressive retinal degeneration [retinitis pigmentosa] mainly affecting rods and peripheral vision (Maw et al. Hum Mol Genet, 2000; Zhang et al. Hum Genet, 2007). A missense mutation of the gene causes dominant macular degeneration, affecting mainly cones and central vision (Yang et al. J Clin Invest, 2008). The features of human progressive retinal degeneration can be phenocopied by a murine prominin-1 gene knockout model (Zacchigna et al. J Neurosci, 2009). Given that the major cell classes and laminar anatomical organization of the vertebrate retina appears to be remarkably conserved during evolution, the retina of lower vertebrate species, e.g. zebrafish (D. rerio), axolotl (A. mexicanum) and chick (G. gallus) offers unique model systems for disentangling problems associated with retinal morphogenesis, degeneration and regeneration. To establish a comparative framework for future functional studies we have isolated and analyzed the retinal distribution of prominin-like genes from lower vertebrate species (fish, axolotl, chick).
Prominin-like genes were cloned from zebrafish, axolotl and chick and their expression was investigated by in situ hybridization in the retina.
In the analyzed species an evolutionarily conserved expression of prominin-1-like molecules was found in photoreceptor cells. Interestingly, the zebrafish genome encodes for two related prominin-1-like genes (co-orthologues), i.e. prominin-like 1a and 1b, showing co-incident expression in photoreceptors and unique, nested expression profile in the inner nuclear layer harbouring among others slowly dividing/quiescent potential stem cells.
Our analysis revealed that not only protein sequences of lower vertebrate prominins show high similarity to their mammalian (mouse, human) counterpart, but also their expression features. Furthermore, our findings suggest a lineage specific sub-functionalization of zebrafish prominin-1 co-orthologues, beside the potential functional redundancy at overlapping sites within the photoreceptor cells. These data will be discussed.
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