Ventralized zebrafish embryo rescue by overexpression of Zic2a

The neuroectoderm arises during gastrulation as a population of undifferentiated proliferating neuroepithelial cells. As development continues, neuroepithelial cells leave the cell cycle and differentiate into neurons and glia of the functioning central nervous system. What processes establish the spatial distribution of proliferating neuroepithelial cells? To investigate this question, zic2a was isolated from zebrafish, a homolog of the Drosophila pair-rule gene odd-paired, which is involved in nervous system patterning. At shield stage, zic2a was expressed in the zebrafish organizer and the blastoderm margin, and became restricted to the axial mesoderm in mid-gastrula. Expression of zic2a appeared in the prospective neuroectoderm during gastrulation, and later demarcated the presumptive forebrain. This expression pattern suggests that zic2a may function early in the organizer and later in the neural plate to demarcate the population of proliferating neuroectoderm. Consistent with a function for zic2a in transducing signals from the organizer, overexpression of zic2a resulted in an expansion of proliferating neuroectoderm. Furthermore, zic2a overexpression rescued the ventralized phenotype of chordino mutant embryos, which lack a functional chordin gene. Early expression of zic2 in the zebrafish organizer, and the phenotype resulting from overexpression, show a role for zic2a downstream of chordin or other secreted organizer proteins in establishing the initial size of the population of neuroectoderm cells.