Antagonistic cross-regulation between Wnt and Hedgehog signalling pathways controls post-embryonic retinal proliferation.
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.
Université Paris-Sud, UPR CNRS 3294, 91405 Orsay, France.
Caroline
C
Borday
Pauline
P
Cabochette
Karine
K
Parain
Nicolas
N
Mazurier
Sylvie
S
Janssens
Hong Thi
HT
Tran
Belaïd
B
Sekkali
Odile
O
Bronchain
Kris
K
Vleminckx
Morgane
M
Locker
Muriel
M
Perron
D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation / Q000187:drug effects; D004336:Drug Antagonism; D004625:Embryo, Nonmammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008954:Models, Biological; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010091:Oximes / Q000494:pharmacology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D013723:Teratogens / Q000494:pharmacology; D014704:Veratrum Alkaloids / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology
C483321:6-bromoindirubin-3'-oxime; D004791:Enzyme Inhibitors; D053823:Hedgehog Proteins; D007211:Indoles; D010091:Oximes; D013723:Teratogens; D014704:Veratrum Alkaloids; C000541:cyclopamine