Xrel3 is required for head development in Xenopus laevis

The Rel/NF-kappaB gene family encodes a large group of transcriptional acti vators involved in myriad differentiation events, including embryonic devel opment. We have shown previously that Xrel3, a Xenopus Rel/NF-kappaB-relate d gene, is expressed in the forebrain, dorsal aspect of the mid- and hindbr ain, the otocysts and notochord of neurula and larval stage embryos. Overex pression of Xrel3 causes formation of embryonic tumours, We now show that X rel3-induced tumours and animal caps from embryos injected with Xrel3 RNA e xpress Otx2, Shh and Gli1, Heterodimerisation of a C-terminally deleted mut ant of Xrel3 with wild-type Xrel3 inhibits in vitro binding of wildtype Xre l3 to Rel/NF-kappaB consensus DNA sequences, This dominant interference mut ant disrupts Shh, Gli1 and Otx2 mRNA patterning and inhibits anterior devel opment when expressed in the dorsal side of zygotes, which is rescued by co -injecting wild-type Xrel3 mRNA, In chick development, Rel activates Shh si gnalling, which is required for normal limb formation; Shh, Gli1 and Otx2 e ncode important neural patterning elements in vertebrates. The activation o f these genes in tumours by Xrel3 overexpression and the inhibition of thei r expression and head development by a dominant interference mutant of Xrel 3 indicates that Rel/NF-kappaB is required for activation of these genes an d for anterior neural patterning in Xenopus.