Several stages in the lens determination process have been defined, th
ough it is not known which gene products control these events. At mid-
gastrula stages in Xenopus, ectoderm is transiently competent to respo
nd to lens-inducing signals. Between late gastrula and neural tube sta
ges, the presumptive lens ectoderm acquires a lens-forming bias, becom
es specified to form lens and begins differentiation. Several genes ha
ve been identified, either by expression pattern, mutant phenotype or
involvement in crystallin gene regulation, that may play a role in len
s bias and specification, and we focus on these roles here. Fate mappi
ng shows that the transcriptional regulators Otx-2, Pax-6 and Sox-3 ar
e expressed in the presumptive lens ectoderm prior to lens differentia
tion. Otx-2 appears first, followed by Pax-6, during the stages of len
s bias (late neural plate stages); expression of Sox-3 follows neural
tube closure and lens specification. We also demonstrate the expressio
n of these genes in competent ectoderm transplanted to the lens-formin
g region, Expression of these genes is maintained or activated prefere
ntially in ectoderm in response to the anterior head environment. Fina
lly, we examined activation of these genes in response to early and la
te lens-inducing signals. Activation of Otx-2, Pax-6 and Sox-3 in comp
etent ectoderm occurs in response to the early inducing tissue, the an
terior neural plate. Since Sox-3 is activated following neural tube cl
osure, we tested its dependence on the later inducing tissue, the opti
c vesicle, which contacts lens ectoderm at this stage. Sox-3 is not ex
pressed in lens ectoderm, nor does a lens form, when the optic vesicle
anlage is removed at late neural plate stages. Expression of these ge
nes demarcates patterning events preceding differentiation and is tigh
tly coupled to particular phases of lens induction.