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 gene that when overexpressed expanded the neural plate at the expense of adjacent neural crest and epidermis. This gene, which we named geminin, had no sequence similarity to known gene families. We later discovered that geminin's neuralizing domain was part of a bifunctional protein whose C-terminal coiled-coil domain may play a role in regulating DNA 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 essential early role in specifying neural cell fate in vertebrates. Maternal geminin mRNA is found throughout the animal hemisphere from oocyte through late blastula. At the early gastrula, however, expression is restricted to a dorsal ectodermal territory that prefigures the neural plate. Misexpression of geminin in gastrula ectoderm suppresses BMP4 expression and converts prospective epidermis into neural tissue. In ectodermal explants, geminin induces expression of the early proneural gene neurogenin-related 1 although not itself being induced by that gene. Later, embryos expressing geminin have an expanded dorsal neural territory and ventral ectoderm is converted to neurons. A putative dominant negative geminin lacking the neuralizing domain suppresses neural differentiation and, when misexpressed dorsally, produces islands of epidermal gene expression within the neurectodermal territory, effects that are rescued by coexpression of the full-length molecule. Taken together, these data indicate that geminin plays an early role in establishing a neural domain during gastrulation.
Kroll
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KL
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. kkroll@bcmp.med.harvard.edu
Salic
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Evans
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Kirschner
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D000595:Amino Acid Sequence; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D002490:Central Nervous System / Q000254:growth & development*; D003001:Cloning, Molecular; D004475:Ectoderm / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D064248:Geminin; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018797:Cell Cycle Proteins; C577998:GMNN protein, Xenopus; D064248:Geminin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus