XENOPUS ZIC-RELATED-1 AND SOX-2, 2 FACTORS INDUCED BY CHORDIN, HAVE DISTINCT ACTIVITIES IN THE INITIATION OF NEURAL INDUCTION

In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor rela ted to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-rela ted HMG factor. Expression of the two genes is first detected widely i n the prospective neuroectoderm at the beginning of gastrulation, foll owing the onset of Chordin expression and preceding that of Neurogenin (Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1 , and initiates neural and neuronal differentiation in isolated animal caps and in vivo, In contrast, Sox-2 alone is not sufficient to cause neural differentiation, but can work synergistically with FGF signali ng to initiate neural induction. Thus, Zic-r1 acts in the pathway brid ging the neural inducer with the downstream proneural genes, while Sox -2 makes the ectoderm responsive to extracellular signals, demonstrati ng that the early phase of neural induction involves simultaneous acti vation of multiple functions.