The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon.
Sox2 is expressed at high levels in neuroepithelial stem cells and persists in neural stem/progenitor cells throughout adulthood. We showed previously that the Sox2 regulatory region 2 (SRR2) drives strong expression in these cells. Here we generated transgenic mouse strains with the beta-geo reporter gene under the control of the SRR2 in order to examine the spatiotemporal function of this regulatory region. We show that the SRR2 functions specifically in neural stem/progenitor cells. However, unlike Nestin 2nd intronic enhancer, the SRR2 shows strong regional specificity functioning only in restricted areas of the telencephalon but not in any other portions of the central nervous system such as the spinal cord. We also show by in vitro clonogenic assay that at least some of these SRR2-functioning cells possess the hallmark properties of neural stem cells. In adult brains, we could detect strong beta-geo expression in the subventricular zone of the lateral ventricle and along the rostral migrating stream where actively dividing cells reside. Chromatin immunoprecipitation assays reveal interactions of POU and Sox factors with SRR2 in neural stem/progenitor cells. Our data also suggest that the specific recruitment of these proteins to the SRR2 in the telencephalon defines the spatiotemporal activity of the enhancer in the developing nervous system.
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241; Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670.
Satoru
S
Miyagi
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241.
Masazumi
M
Nishimoto
Department of Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670.
Tetsuichiro
T
Saito
Department of Physiology, Keio University School of Medicine, Shinjyuku-ku, Tokyo 160-8582, Japan; Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Shinjyuku-ku, Tokyo 160-8582, Japan.
Mikiko
M
Ninomiya
Department of Physiology, Keio University School of Medicine, Shinjyuku-ku, Tokyo 160-8582, Japan; Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Shinjyuku-ku, Tokyo 160-8582, Japan.
Kazunobu
K
Sawamoto
Department of Physiology, Keio University School of Medicine, Shinjyuku-ku, Tokyo 160-8582, Japan.
Hideyuki
H
Okano
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241.
Masami
M
Muramatsu
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670.
Hideyuki
H
Oguro
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670.
Atsushi
A
Iwama
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241; REDS Group, Saitama Small Enterprise Promotion Corp., Skip City, Kawaguchi, Saitama 333-0844, Japan. Electronic address: akiokuda@saitama-med.ac.jp.
Akihiko
A
Okuda
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D050809:POU Domain Factors / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050809:POU Domain Factors; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D015534:Trans-Activators