GEMININ, A NEURALIZING MOLECULE THAT DEMARCATES THE FUTURE NEURAL PLATE AT THE ONSET OF GASTRULATION

In an expression cloning screen in Xenopus embryos, we identified a ge ne that when overexpressed expanded the neural plate at the expense of adjacent neural crest and epidermis, This gene, which we named gemini n, had no sequence similarity to known gene families. We later discove red that geminin's neuralizing domain was part of a bifunctional prote in whose C-terminal coiled-coil domain may play a role in regulating D NA replication. We report here on the neuralizing function of geminin, The localization, effect of misexpression and activity of a dominant negative geminin suggest that the product of this gene has an essentia l early role in specifying neural cell fate in vertebrates. Maternal g eminin mRNA is found throughout the animal hemisphere from oocyte thro ugh late blastula, At the early gastrula, however expression is restri cted to a dorsal ectodermal territory that prefigures the neural plate . Misexpression of germinin in gastrula ectoderm suppresses BMP4 expre ssion and converts prospective epidermis into neural tissue. In ectode rmal explants, geminin induces expression of the early proneural gene neurogenin-related I although not itself being induced by that gene. L ater, embryos expressing geminin have an expanded dorsal neural territ ory and ventral ectoderm is converted to neurons. A putative dominant negative geminin lacking the neuralizing domain suppresses neural diff erentiation and, when misexpressed dorsally, produces islands of epide rmal gene expression within the neurectodermal territory, effects that are rescued by coexpression of the full-length molecule. Taken togeth er, these data indicate that geminin plays an early role in establishi ng a neural domain during gastrulation.