title: XBF-2 is a transcriptional repressor that converts ectoderm into neural tissue.
abstract: We have identified Xenopus Brain Factor 2 (XBF-2) as a potent neuralizing activity in an expression cloning screen. In ectodermal explants, XBF-2 converts cells from an epidermal to a neural fate. Such explants contain neurons with distinct axonal profiles and express both anterior and posterior central nervous system (CNS) markers. In striking contrast to X-ngnR-1a or X-NeuroD, ectopic expression of XBF-2 in Xenopus embryos results in an expansion of the neural plate to the ventral midline. The enlarged neural plate consists predominantly of undifferentiated neurons. XBF-2 lies downstream of the BMP antagonists noggin, cerberus, and gremlin since ectodermal explants expressing these molecules exhibit strong expression of XBF-2. While XBF-2 does not upregulate the expression of secreted neural inducers, it downregulates the transcription of BMP-4, an epidermal inducer. We show that XBF-2 acts as a transcriptional repressor and that its effects can be phenocopied with either the engrailed or hairy repressor domain fused to the XBF-2 DNA-binding domain. A fusion of the DNA-binding domain to the activator domain of VP16 blocks the effects of XBF-2 and prevents neural plate development in the embryo. This provides evidence that a transcriptional repressor can affect both regional neural development and neurogenesis in vertebrates.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: F V
authors.initials: FV
authors.lastname: Mariani
authors.forename: R M
authors.initials: RM
authors.lastname: Harland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019556:COS Cells; D002454:Cell Differentiation; D002490:Central Nervous System / Q000254:growth & development; D004268:DNA-Binding Proteins / Q000235:genetics*; D004475:Ectoderm / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008845:Microinjections; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection / Q000235:genetics; D014981:Xenopus / Q000196:embryology* / Q000254:growth & development
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors