title: Intrinsic transition of embryonic stem-cell differentiation into neural progenitors.
abstract: The neural fate is generally considered to be the intrinsic direction of embryonic stem (ES) cell differentiation. However, little is known about the intracellular mechanism that leads undifferentiated cells to adopt the neural fate in the absence of extrinsic inductive signals. Here we show that the zinc-finger nuclear protein Zfp521 is essential and sufficient for driving the intrinsic neural differentiation of mouse ES cells. In the absence of the neural differentiation inhibitor BMP4, strong Zfp521 expression is intrinsically induced in differentiating ES cells. Forced expression of Zfp521 enables the neural conversion of ES cells even in the presence of BMP4. Conversely, in differentiation culture, Zfp521-depleted ES cells do not undergo neural conversion but tend to halt at the epiblast state. Zfp521 directly activates early neural genes by working with the co-activator p300. Thus, the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the cell-intrinsic expression and activator function of Zfp521.
authors.affiliation: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamiya
authors.forename: Satoe
authors.initials: S
authors.lastname: Banno
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sasai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ohgushi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Inomata
authors.forename: Kiichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Masako
authors.initials: M
authors.lastname: Kawada
authors.forename: Rieko
authors.initials: R
authors.lastname: Yakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakao
authors.forename: Lars Martin
authors.initials: LM
authors.lastname: Jakt
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005855:Germ Layers / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D054258:Neural Plate / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014981:Xenopus; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D015820:Cadherins; C472572:Evi3 protein, mouse; D055748:SOXB1 Transcription Factors; C098693:Sox1 protein, mouse; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors