Katsunori Nakata

Physical and Functional Interactions between Zic and Gli Proteins

Zic and Gli family proteins are transcription factors that share similar zinc finger domains. Recent studies indicate that Zic and Gli collaborate in neural and skeletal development. We provide evidence that the Zic and Gli proteins physically and functionally interact through their zinc finger domains. Moreover, Gli proteins were translocated to cell nuclei by coexpressed Zic proteins, and both proteins regulated each others transcriptional activity. Our result suggests that the physical interaction between Zic and Gli is the molecular basis of their antagonistic or synergistic features in developmental contexts and that Zic proteins are potential modulators of the hedgehog-mediated signaling pathway.

A novel member of the Xenopus Zic family, Zic5, mediates neural crest development

We characterized Xenopus Zic5 which belongs to a novel class of the Zic family. Zic5 is more specifically expressed in the prospective neural crest than other Zic genes. Overexpression of Zic5 in embryos led to ectopic expression of the early neural crest markers, Xsna and Xslu, with the loss of epidermal marker expression. In Zic5-overexpressing animal cap explants, there was marked induction of neural crest markers, without mesodermal and anterior neural markers. This was in contrast to other Xenopus Zic genes, which induce both anterior and the neural crest markers in the same assay. Injection of a dominant-negative form of Zic5 can block neural crest formation in vivo. These results indicate that Zic5 expression converts cells from an epidermal fate to a neural crest cell fate. This is the first evidence for neural crest tissue inductive activity separate from anterior neural tissue inductive activity in a Zic family gene.

Xenopus Polycomblike 2 (XPcl2) controls anterior to posterior patterning of the neural tissue

Abstract. A novel gene, Xenopus Polycomblike 2 (XPcl2), which encodes a protein similar to Drosophila Polycomblike was cloned and characterized. Polycomblike belongs to the Polycomb group proteins, which maintain stable expression patterns for the clustered homeotic genes in the Drosophila embryo by forming multimeric complexes on chromatin. XPcl2 shows greater amino acid sequence homology to human and mouse M96 (hPcl2, mPcl2) than Xenopus Pcl1 (XPcl1), mouse Tctex3 (mPcl1) and human PHF1 (hPcl1), indicating that at least two types of Polycomblike genes are conserved between amphibians and mammals. XPcl2 mRNA is present both maternally and zygotically, and the temporal expression profile is distinct from XPcl1, another member of the Polycomblike family in Xenopus. XPcl2 is highly expressed in the anterior-dorsal region of Xenopus following the neurula stage in a manner similar to XPcl1. Overexpression of XPcl2 disturbs the development of the anterior central nervous system, eye and cement gland. In the XPcl2-overexpressing embryo, a hindbrain marker, Krox20, and a spinal cord marker, HoxB9, are expressed more posteriorly, suggesting an alteration in the anterior-posterior patterning of the neural tissue. In addition, XPcl2 represses Zic3- and noggin-induced anterior neural markers, but not neural crest markers in animal cap explants. These results indicate that XPcl2 regulates anterior neural tissue development and the anterior-posterior patterning of the neural tissue.

Roles of Zic family in neural development

Vertebrate nervous systems are formed from embryonic ectoderm by complicated tissue interactions during early embryogenesis. Most importantly, the signals emanating from the organizer (Neural inducer) play a crutial role in this process. Recent studies using molecular techniques have identified several organizer-derived neural inducers in Xenopus We isolated the neural inducer Chrodin which can induce neural differentiation in isolated embryonic ectoderm. Chordin functions by antagonizing the anineuralizing factor BMP-4. In this talk, I would like to review recent progress in neural induction reseach. In addition, our recent data on downstream factors of Chordin and their roles in the forming CNS

1040 Xzic3, a primary regulator both in neural and neural crest development

YASUFUMI SATO, TATSUMI HIRATA, HAJIME FUJISAWA During development, mitral cell axons, the main efferents of the olfac tory bulb grow into a very narrow part of the telencephalon and form the lateral olfactory tract (LOT). We previously suggested that intrinsic cells of the telencephalon play a role in guiding mitral cell axons. In this study, we show that monoclonal antibody lot1 which was produced against the olfactory cortex recognizes a subset of neurons which are distributed along the LOT. The lotl-positive neurons are observed from the stage E12.0 which is well before mitral cell axons grow out of the olfactory bulb. The first mitral cell axons elongate just above the lotl-positive neurons and form the primitive LOT. In organotypic cocultures, mitral cell axons also choose regions where the lotl-positive neurons are located for their elongation. These results suggest that the lotl-positive neurons are involved in axonal projection of mitral cells.