Pax6-5a Promotes Neuronal Differentiation of Murine Embryonic Stem Cells

Nao Shimizu; Hajime Watanabe; Junko Kubota; Jinzhan Wu; Ryota Saito; Tadashi Yokoi; Takumi Era; Takeshi Iwatsubo; Takashi Watanabe; Sachiko Nishina; Noriyuki Azuma; Toshiaki Katada; Hiroshi Nishina

doi:10.1248/bpb.32.999

Regular Articles

Pax6-5a Promotes Neuronal Differentiation of Murine Embryonic Stem Cells

Nao Shimizu, Hajime Watanabe, Junko Kubota, Jinzhan Wu, Ryota Saito, Tadashi Yokoi, Takumi Era, Takeshi Iwatsubo, Takashi Watanabe, Sachiko Nishina, Noriyuki Azuma, Toshiaki Katada, Hiroshi Nishina

Author information

Nao Shimizu
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
Hajime Watanabe
Center for Integrative Bioscience, Okazaki National Research Institutes
Junko Kubota
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
Jinzhan Wu
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
Ryota Saito
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
Tadashi Yokoi
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University
Department of Ophthalmology, National Center for Child Health and Development
Takumi Era
Department of Organogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University
Takeshi Iwatsubo
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo
Takashi Watanabe
Department of Laboratory Medicine, Kyorin University School of Medicine
Sachiko Nishina
Department of Ophthalmology, National Center for Child Health and Development
Noriyuki Azuma
Department of Ophthalmology, National Center for Child Health and Development
Toshiaki Katada
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo
Hiroshi Nishina
Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University

Keywords: Pax6, Pax6-5a, embryonic stem cell, neuron, DNA microarray, basic helix loop–helix domain containing, class b2

JOURNAL FREE ACCESS

2009 Volume 32 Issue 6 Pages 999-1003

DOI https://doi.org/10.1248/bpb.32.999

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Abstract

Pax6 genes are highly conserved and important for eye development. Vertebrates predominantly produce two alternatively spliced Pax6 isoforms, Pax6 and Pax6-5a. Pax6-5a differs from Pax6 by the presence of 14 additional amino acids encoded by exon 5a. These additional amino acids occur in the Pax6 paired domain and thus influence its DNA-binding properties. However, little is known about Pax6-5a's physiological functions. Here we establish murine embryonic stem (ES) cell lines in which expression of either the human Pax6 or Pax6-5a isoform is negatively controlled by tetracycline. We report that, in contrast to Pax6 expression, Pax6-5a expression strongly induces ES cells to differentiate into neurons. Moreover, using DNA microarray analysis, we have identified the transcription factor basic helix loop–helix domain containing, class b2 (bHLHb2) in Pax6-5a-expressing ES cells. Our Pax6 isoform-expressing ES cell lines may serve as useful models for identifying Pax6-regulated genes that are important for neurogenesis and/or eye development.

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