Wnt ligands from the embryonic surface ectoderm regulate 'bimetallic strip' optic cup morphogenesis in mouse.

Development 2015 Mar;142(5):972-82

Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA

The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wls(fl/fl)) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wls(fl/fl) mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change.

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.120022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352985PMC
March 2015

Publication Analysis

Top Keywords

optic cup
16
surface ectoderm
12
wnt ligands
12
le-cre wlsfl/fl
8
wnt/β-catenin response
8
wnt/β-catenin pathway
8
rpe cells
4
shared features
4
features produced
4
phenotype shared
4
mesenchyme phenotype
4
periocular mesenchyme
4
cells reduced
4
produced wnt/β-catenin
4
wnt
4
lrp6 mutated
4
mutated retinoic
4
mice numbers
4
co-receptor lrp6
4
numbers rpe
4

Similar Publications