Lens morphogenesis is dependent on Pax6-mediated inhibition of the canonical Wnt/beta-catenin signaling in the lens surface ectoderm.
Lens formation in mouse is critically dependent on proper development of the retinal neuroectoderm that is located close beneath the head surface ectoderm. Signaling from the prospective retina triggers lens-specific gene expression in the surface-ectoderm. Supression of canonical Wnt/beta-catenin signaling in the surface ectoderm is one of the prerequisites for lens development because, as we show here, ectopic Wnt activation in the retina and lens abrogates lens formation. Wnt inhibiton is mediated by signals coming from the retina but its exact mechanism is unknown. We show that Pax6 directly controls expression of several Wnt inhibitors such as Sfrp1, Sfrp2, and Dkk1 in the presumptive lens. In accordance, absence of Pax6 function leads to aberrant canonical Wnt activity in the presumptive lens that subsequently impairs lens development. Thus Pax6 is required for down-regulation of canonical Wnt signaling in the presumptive lens ectoderm.
Machon
Ondrej
O
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 14420 Prague 4, Czech Republic.
Kreslova
Jana
J
Ruzickova
Jana
J
Vacik
Tomas
T
Klimova
Lucie
L
Fujimura
Naoko
N
Lachova
Jitka
J
Kozmik
Zbynek
Z
D000818:Animals; D004475:Ectoderm / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007908:Lens, Crystalline / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin