Background: The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). It is not clear, however, which progenitors are multipotent or why they are multipotent.

Wnt proteins can activate different intracellular signaling cascades in various organisms by interacting with receptors of the Frizzled family. The first identified Wnt signaling pathway, the Wnt/beta-catenin pathway, has been studied in much detail and is highly conserved among species. As to non-canonical Wnt pathways, the current situation is more nebulous partly because the intracellular mediators of this pathway are not yet fully understood and, in some cases, even identified. However, there are increasing data that prove the existence of non-canonical Wnt signaling and demonstrate its involvement in different developmental processes. In vertebrates, Wnt-11 and Wnt-5A can activate the Wnt/JNK pathway, which resembles the planar cell polarity pathway in Drosophila. The Wnt/Ca(2+)-pathway has only been described in Xenopus and zebrafish so far and it is unclear whether it also exists in other organisms. Two recent papers provide us with new insight into non-canonical Wnt signaling by (1) presenting a new intracellular mediator of non-canonical signaling in Xenopus1 and (2) implicating the existence of an additional non-canonical Wnt signaling pathway in flies.

Wnt-4 is expressed in developing neural and renal tissue and is required for renal tubulogenesis in mouse and Xenopus. The function of Wnt-4 in neural differentiation is unknown so far. Here we demonstrate that Wnt-4 is required for eye development in Xenopus laevis. This effect of Wnt-4 depends on the activation of a b-catenin-independent, noncanonical Wnt signaling pathway. Furthermore, we report the identification of EAF2, a component of the ELL-mediated RNA polymerase II elongation factor complex, as a target gene of Wnt-4 signaling. EAF2 is specifically expressed in the eye and EAF2 expression was dependent on Wnt-4 function. Loss of EAF2 function results in loss of eyes and loss of Wnt-4 function could be rescued by EAF2. In neuralized animal caps, EAF2 has properties characteristic for an RNA polymerase II elongation factor regulating the expression of the eye-specific transcription factor Rx. These data add a new layer of complexity to our understanding of eye development and give further evidence for the importance of noncanonical Wnt pathways in organ development.

Pescadillo is a multifunctional, nuclear protein involved in rRNA precursor processing, ribosomal assembly, and transcriptional regulation. Pescadillo has been assigned important functions in embryonic development and tumor formation. We previously identified pescadillo as a potential downstream target of non-canonical Wnt-4 signaling. Here we have investigated for the first time the function of the Xenopus laevis homolog of pescadillo during early embryogenesis on a molecular level. Loss of function analysis indicates that pescadillo is required for eye development and neural crest migration. BrdU incorporation and TUNEL assays indicate that a loss of pescadillo function affects proliferation and triggers apoptosis through a p53-mediated mechanism. Furthermore, pescadillo affects the expression of early eye-specific marker genes, likely independent of its function in regulating proliferation and apoptosis, and in addition migration of cranial neural crest cells. Our data indicate that pescadillo has multiple important functions during X. laevis development and that its function is highly conserved among different species.