Amphibian Zic Genes

Studies in Xenopus laevis have greatly contributed to understanding the roles that the Zic family of zinc finger transcription factors play as essential drivers of early development. Explant systems that are not readily available in other organisms give Xenopus embryos a unique place in these studies, facilitated by the recent sequencing of the Xenopus laevis genome. A number of upstream regulators of zic gene expression have been identified, such as inhibition of BMP signaling, as well as calcium, FGF, and canonical Wnt signaling. Screens using induced ectodermal explants have identified genes that are direct targets of Zic proteins during early neural development and neural crest specification. These direct targets include Xfeb (also called glipr2; hindbrain development), aqp3b (dorsal marginal zone in gastrula embryos and neural folds), snail family members (premigratory neural crest), genes that play roles in retinoic acid signaling, noncanonical Wnt signaling, and mesoderm development, in addition to a variety of genes some with and many without known roles during neural or neural crest development. Functional experiments in Xenopus embryos demonstrated the involvement of Zic family members in left-right determination, early neural patterning, formation of the midbrain-hindbrain boundary, and neural crest specification. The role of zic genes in cell proliferation vs. differentiation remains unclear, and the activities of Zic factors as inhibitors or activators of canonical Wnt signaling may be dependent on developmental context. Overall, Xenopus has contributed much to our understanding of how Zic transcriptional activities shape the development of the embryo and contribute to disease.