Publication Date:
2011-02-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamiya, Daisuke -- Banno, Satoe -- Sasai, Noriaki -- Ohgushi, Masatoshi -- Inomata, Hidehiko -- Watanabe, Kiichi -- Kawada, Masako -- Yakura, Rieko -- Kiyonari, Hiroshi -- Nakao, Kazuki -- Jakt, Lars Martin -- Nishikawa, Shin-ichi -- Sasai, Yoshiki -- England -- Nature. 2011 Feb 24;470(7335):503-9. doi: 10.1038/nature09726. Epub 2011 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21326203" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bone Morphogenetic Protein 4/deficiency/genetics/metabolism
;
Cadherins/metabolism
;
*Cell Differentiation
;
Cell Lineage
;
Cells, Cultured
;
Embryo, Mammalian/cytology/embryology/metabolism
;
Embryonic Stem Cells/*cytology/metabolism
;
Gene Expression Regulation, Developmental/genetics
;
Germ Layers/cytology/embryology/metabolism
;
HEK293 Cells
;
Humans
;
Mice
;
Models, Biological
;
Neural Plate/cytology/embryology/metabolism
;
Neural Stem Cells/*cytology/metabolism
;
Oligonucleotide Array Sequence Analysis
;
SOXB1 Transcription Factors/metabolism
;
Transcription Factors/deficiency/genetics/*metabolism
;
Transcriptional Activation
;
Xenopus
;
p300-CBP Transcription Factors/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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