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Development October 1, 2012; 139 (19): 3499-509.

Antagonistic cross-regulation between Wnt and Hedgehog signalling pathways controls post-embryonic retinal proliferation.

Borday C , Cabochette P , Parain K , Mazurier N , Janssens S , Tran HT , Sekkali B , Bronchain O , Vleminckx K , Locker M , Perron M .

Continuous neurogenesis in the adult nervous system requires a delicate balance between proliferation and differentiation. Although Wnt/β-catenin and Hedgehog signalling pathways are thought to share a mitogenic function in adult neural stem/progenitor cells, it remains unclear how they interact in this process. Adult amphibians produce retinal neurons from a pool of neural stem cells localised in the ciliary marginal zone (CMZ). Surprisingly, we found that perturbations of the Wnt and Hedgehog pathways result in opposite proliferative outcomes of neural stem/progenitor cells in the CMZ. Additionally, our study revealed that Wnt and Hedgehog morphogens are produced in mutually exclusive territories of the post-embryonic retina. Using genetic and pharmacological tools, we found that the Wnt and Hedgehog pathways exhibit reciprocal inhibition. Our data suggest that Sfrp-1 and Gli3 contribute to this negative cross-regulation. Altogether, our results reveal an unexpected antagonistic interplay of Wnt and Hedgehog signals that may tightly regulate the extent of neural stem/progenitor cell proliferation in the Xenopus retina.

PubMed ID: 22899850
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: ccnd1 ctnnb1 dhh gli1 gli3 ihh ptch1 rlbp1 rpe sfrp1 shh tcf7l1 wnt16 wnt2b wnt3a wnt7b wnt8b wnt9a wnt9b
Morpholinos: gli3 MO2 sfrp1 MO3

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