RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling.
The retinal pigment epithelium (RPE) is indispensable for vertebrate eye development and vision. In the classical model of optic vesicle patterning, the surface ectoderm produces fibroblast growth factors (FGFs) that specify the neural retina (NR) distally, whereas TGFβ family members released from the proximal mesenchyme are involved in RPE specification. However, we previously proposed that bone morphogenetic proteins (BMPs) released from the surface ectoderm are essential for RPE specification in chick. We now show that the BMP- and Wnt-expressing surface ectoderm is required for RPE specification. We reveal that Wnt signalling from the overlying surface ectoderm is involved in restricting BMP-mediated RPE specification to the dorsal optic vesicle. Wnt2b is expressed in the dorsal surface ectoderm and subsequently in dorsal optic vesicle cells. Activation of Wnt signalling by implanting Wnt3a-soaked beads or inhibiting GSK3β at optic vesicle stages inhibits NR development and converts the entire optic vesicle into RPE. Surface ectoderm removal at early optic vesicle stages or inhibition of Wnt, but not Wnt/β-catenin, signalling prevents pigmentation and downregulates the RPE regulatory gene Mitf. Activation of BMP or Wnt signalling can replace the surface ectoderm to rescue MITF expression and optic cup formation. We provide evidence that BMPs and Wnts cooperate via a GSK3β-dependent but β-catenin-independent pathway at the level of pSmad to ensure RPE specification in dorsal optic vesicle cells. We propose a new dorsoventral model of optic vesicle patterning, whereby initially surface ectoderm-derived Wnt signalling directs dorsal optic vesicle cells to develop into RPE through a stabilising effect of BMP signalling.
Fachgebiet Entwicklungsbiologie und Neurogenetik, Technische Universität Darmstadt, Schnittspahnstrasse 13, D-64287 Darmstadt, Germany.
Jörg
J
Steinfeld
Ichie
I
Steinfeld
Nicola
N
Coronato
Meggi-Lee
ML
Hampel
Paul G
PG
Layer
Masasuke
M
Araki
Astrid
A
Vogel-Höpker
D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002642:Chick Embryo; D004475:Ectoderm / Q000166:cytology*; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis; D055213:Retinal Pigment Epithelium / Q000196:embryology* / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D051739:Microphthalmia-Associated Transcription Factor; D051785:Smad Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
Cell fate; Eye; Gsk3β; Mitf; Optic cup; Optic vesicle patterning; Retinal development; Smad; Vsx2