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The Journal of Neuroscience, October 19, 2005, 25(42):9752-9761; doi:10.1523/JNEUROSCI.2512-05.2005

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Development/Plasticity/Repair
Role of Fabp7, a Downstream Gene of Pax6, in the Maintenance of Neuroepithelial Cells during Early Embryonic Development of the Rat Cortex

Yoko Arai,¹ Nobuo Funatsu,² Keiko Numayama-Tsuruta,¹ Tadashi Nomura,¹ Shun Nakamura,² and Noriko Osumi^1,3

¹Division of Developmental Neuroscience, Department of Functional Genomics, Center for Translational and Advanced Animal Research, Tohoku University School of Medicine, Aoba-ku, Sendai 980-8575, Japan, ²Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan, and ³Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, 332-0012, Japan

Pax6 is a transcription factor with key functional roles in the developing brain. Pax6 promotes neuronal differentiation via transcriptional regulation of the Neurogenin2 (Ngn2) gene, although Pax6 expression appears in proliferating neuroepithelial cells before the onset of neurogenesis. Here, we identified Fabp7 (BLBP/B-FABP), a member of the fatty acid-binding protein (FABP) family, as a downregulated gene in the embryonic brain of Pax6 mutant rat (rSey²/rSey²) by microarray analysis. Marked reduction of Fabp7 expression was confirmed by quantitative PCR. Spatiotemporal expression patterns of Fabp7 in the wild-type rat embryos from embryonic day 10.5 (E10.5) to E14.5 were similar to those of Pax6, and expression of Fabp7 was undetectable in the rSey²/rSey² cortex. The expression pattern of Fabp7 in the wild-type mouse embryo at E10.5 (corresponding to E12.5 rat) was different from that in the rat embryo, and no change of expression was observed in the Sey/Sey mouse embryo. Overexpression of exogenous Pax6 mainly induced ectopic expression of Fabp7, rather than of Ngn2, in the early cortical primordium. Interestingly, knocking-down FABP7 function by electroporation of Fabp7 small interfering RNA severely curtailed cell proliferation but promoted neuronal differentiation. We conclude that Fabp7 is a downstream gene of Pax6 transcription factor in the developing rat cortex and essential for maintenance of neuroepithelial cells during early cortical development.

Key words: Pax6; Fabp7; microarray; Small eye rat; siRNA; neurogenesis

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Received June 19, 2005; revised September 11, 2005; accepted September 11, 2005.

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