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 a survey of Wnt expression, we did not find any Wnt transcripts present in migrating NCCs. However, we did find a strong correlation between NCC migration and Wnt2b expression in the ectoderm: following contact with migrating NCCs, Wnt2b began to be expressed in the neighbouring ectoderm but remained absent from the prospective lens territory (Fig. 3a–c). The highest levels of Axin2 expression (a read-out of canonical Wnt activity) were present in ectoderm that had been in contact with NCCs for longest duration (Fig. 3d,e, arrowheads; compare midbrain and forebrain levels). These observations suggest that NCCs initiate Wnt2b expression in the ectoderm in which lens formation is normally inhibited. Indeed, migratory NCCs strongly induced Wnt2b in presumptive lens explants, which normally do not express the transcript (Fig. 3f,g), suggesting that TGF-β may be the NCC signal responsible for ectodermal Wnt2b. Indeed, in vitro, Wnt2b induction by NCCs failed when TGF-β signalling was inhibited (Fig. 3h), whereas Activin A strongly induced Wnt2b in presumptive lens explants (Fig. 3i,j). Similarly, in vivo, ectodermal Wnt2b expression depended on TGF-β signalling from NCCs: NCC ablation (Fig. 3k,l) and misexpression of the inhibitory Smad7 (Fig. 3m,n; Smad7: 2/6 Wnt2b+, green fluorescent protein: 5/5 Wnt2b+) caused downregulation of Wnt2b transcripts in the non-lens ectoderm. Together, these results show that TGF-β signalling from NCCs induces Wnt2b expression in the non-lens ectoderm.
Affiliation: Department of Craniofacial Development, King's College London, Guy's Campus, London SE1 9RT, UK.