Letter abstract
Nature Cell Biology 9, 72 - 79 (2006)
Published online: 10 December 2006 | doi:10.1038/ncb1521
There is a Corrigendum (April 2007) associated with this Letter.
Triggering neural differentiation of ES cells by subtype switching of importin-
Noriko Yasuhara1, Noriko Shibazaki1, Shinya Tanaka2, Masahiro Nagai1, Yasunao Kamikawa3, Souichi Oe1, Munehiro Asally3, Yusuke Kamachi2, Hisato Kondoh2 & Yoshihiro Yoneda1,3
Nuclear proteins are selectively imported into the nucleus by transport factors such as importin-
and importin-
1, 2. Here, we show that the expression of importin- subtypes is strictly regulated during neural differentiation of mouse embryonic stem (ES) cells, and that the switching of importin- subtype expression is critical for neural differentiation. Moreover, reproducing the switching of importin- subtype expression in undifferentiated ES cells induced neural differentiation in the presence of leukaemia inhibitory factor (LIF) and serum, coordinated with the regulated expression of Oct3/4, Brn2 and SOX2, which are involved in ES–neural identity determination. These transcription factors were selectively imported into the nucleus by specific subtypes of importin-. Thus, importin- subtype switching has a major impact on cell differentiation through the regulated nuclear import of a specific set of transcription factors. This is the first study to propose that transport factors should be considered as major players in cell-fate determination.
- Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
- Developmental Biology Group, Graduate School of Frontier Biosciences, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
- Biomolecular Dynamics Group, Graduate School of Frontier Biosciences, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Correspondence to: Yoshihiro Yoneda1,3 e-mail: yyoneda@anat3.med.osaka-u.ac.jp
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