Neural crest cells organize the eye via TGF-β and canonical Wnt signalling.
Bottom Line: In vertebrates, the lens and retina arise from different embryonic tissues raising the question of how they are aligned to form a functional eye.Here we show, using the chick as a model system, that neural crest-derived transforming growth factor-βs activate both Smad3 and canonical Wnt signalling in the adjacent ectoderm to position the lens next to the retina.They do so by controlling Pax6 activity: although Smad3 may inhibit Pax6 protein function, its sustained downregulation requires transcriptional repression by Wnt-initiated β-catenin.
Affiliation: Department of Craniofacial Development, King's College London, Guy's Campus, London SE1 9RT, UK.Show MeSH
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Mentions: In mouse, canonical Wnt signalling suppresses lens development20. Consistent with this, we found that overexpression of constitutively active β-catenin in PLE prevented the expression of δ-crystallin. Although 83% of control cells were δ-crystallin+ (66/87 cells in three lenses; Fig. 2a–c), this was reduced to 35% when canonical Wnt signalling was activated (27/77 cells in five lenses; Fig. 2d–j). Interestingly, similar to caSmad3-expressing cells (Fig. 1d–f), those carrying β-catenin were excluded from the lens over time: after 24 h β-catenin+/δ-crystallin− cells were found in the lens placode (Fig. 2d–f), but were mostly absent from the lens after 48 h (Fig. 2g–i). If Wnt signalling is involved in the residual lens-repressing activity of NCCs, Wnt inhibition should rescue lens development in the presence of NCCs. To test this, we cocultured NCCs and PLE with the Wnt antagonist N-Fz8. Indeed, inhibition of Wnt signalling rescued δ-crystallin expression (Fig. 2k–m), suggesting that Wnt is required for lens repression by NCCs and suppresses lens formation through β-catenin (Fig. 2n).
Affiliation: Department of Craniofacial Development, King's College London, Guy's Campus, London SE1 9RT, UK.