A large scale screen for neural stem cell markers in Xenopus retina

Abstract

Neural stem cell research suffers from a lack of molecular markers to specifically assess stem or progenitor cell properties. The organization of the Xenopus ciliary marginal zone (CMZ) in the retina allows the spatial distinction of these two cell types: stem cells are confined to the most peripheral region, while progenitors are more central. Despite this clear advantage, very few genes specifically expressed in retinal stem cells have been discovered so far in this model. To gain insight into the molecular signature of these cells, we performed a large-scale expression screen in the Xenopus CMZ, establishing it as a model system for stem cell gene profiling. Eighteen genes expressed specifically in the CMZ stem cell compartment were retrieved and are discussed here. These encode various types of proteins, including factors associated with proliferation, mitotic spindle organization, DNA/RNA processing, and cell adhesion. In addition, the publication of this work in a special issue on Xenopus prompted us to give a more general illustration of the value of large-scale screens in this model species. Thus, beyond neural stem cell specific genes, we give a broader highlight of our screen outcome, describing in particular other retinal cell markers that we found. Finally, we present how these can all be easily retrieved through a novel module we developed in the web-based annotation tool XenMARK, and illustrate the potential of this powerful searchable database in the context of the retina.

Zebrafish midbrain slow-amplifying progenitors exhibit high levels of transcripts for nucleotide and ribosome biogenesis

“…Transcripts encoding Nop56/58 are signatures of fish PML progenitors (this study), but also of the fish (Fig. 5) and Xenopus (Parain et al, 2011) retina. The Wdr12, Pes and Bop1 proteins are associated with PeBoW, a complex crucial for the maturation of the large ribosomal subunits in mammalian cells (Hölzel et al, 2005).…”

A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation

“…6D). The very peripheral cells of the CMZ additionally express the hairy and enhancer-of-split ( hes ) genes hes1 and hes4 , which are believed to be markers of retinal stem cells (Parain et al, 2012; El Yakoubi et al, 2012). Following ND, expression of hes1 and hes4 remained high in the peripheral CMZ (Fig.…”

Hes4 Controls Proliferative Properties of Neural Stem Cells During Retinal Ontogenesis

“…Comprehensive analysis of RSC ontogeny and properties necessitates reliable markers to formally identify these immature cells within proliferating heterogeneous cell populations in vivo . To gain insight into the molecular signature of RSCs, we recently performed a large-scale expression screen in the Xenopus CMZ [14]. Among identified RSC markers, we retrieved the Hes4 gene (previously known as XHairy2 in Xenopus and ortholog of zebrafish Her9 and chick cHairy1 ) that encodes a transcriptional repressor of the bHLH-O family.…”