Fig. 7. A model of FoxE3 activation in Xenopus. (A) Integration of Otx2 and Notch inputs on the FoxE3 enhancer. Otx2 and Su(H) are proposed to bind to the FoxE3 enhancer prior to receiving Notch signaling, but remain in a quiescent state. In response to stimuli from Delta ligands, the Notch intracellular domain (NICD) is cleaved from its extracellular domain and translocated into the nucleus. Although this model shows a direct interaction between membrane-bound Notch and Delta, we do not know the exact mechanism by which this signaling may occur in this system (see Discussion). In the nucleus, NICD forms a complex with Su(H) and activates transcription by recruiting a co-activator (Co-A). Otx2 synergistically stimulates this transcription. An unidentified factor(s) (indicated with a question mark) may contribute to boosting and refining the PLE-specific expression. (B) Otx2 is broadly expressed in the head ectoderm that includes PLE, while localized Notch signaling is provided to the lens-field from the underlying optic vesicle (upper). FoxE3 is expressed in the PLE, which is the region where there is both Otx2 expression and Notch signaling (beneath).