Zhao, H., Tanegashima, K., Ro, H., and Dawid, I.B. (2008) Lrig3 regulates neural crest formation in Xenopus by modulating Fgf and Wnt signaling pathways. Development (Cambridge, England). 135(7):1283-1293.
Leucine-rich repeats and immunoglobulin-like domains 3
(Lrig3) was identified by microarray analysis among genes that show
differential expression during gastrulation in Xenopus laevis.
Lrig3 was expressed in the neural plate and neural crest (NC) at
neurula stages, and in NC derivatives and other dorsal structures during
tailbud stages. A prominent consequence of the morpholino-induced inhibition
of Lrig3 expression was impaired NC formation, as revealed by the suppression
of marker genes, including Slug, Sox9 and Foxd3. In
the NC induction assay involving Chordin plus Wnt3a-injected
animal caps, Lrig3 morpholino inhibited expression of Slug, Sox9
and Foxd3, but not of Pax3 and Zic1. In line with this,
Lrig3 knockdown prevented NC marker induction by Pax3 and
Zic1, suggesting that Lrig3 acts downstream of these two
genes in NC formation. Injection of Lrig3 and Wnt3a led to
low-level induction of NC markers and enhanced induction of Fgf3,
Fgf4 and Fgf8 in animal caps, suggesting a positive role for
Lrig3 in Wnt signaling. Lrig3 could attenuate Fgf signaling in animal caps,
did interact with Fgf receptor 1 in cultured cells and, according to context,
decreased or increased the induction of NC markers by Fgf. We suggest that
Lrig3 functions in NC formation in Xenopus by modulating the Wnt and
Fgf signaling pathways.