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The Journal of Neuroscience, October 8, 2008, 28(41):10415-10421; doi:10.1523/JNEUROSCI.3219-08.2008

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Brief Communications
MicroRNA-9 Modulates Cajal–Retzius Cell Differentiation by Suppressing Foxg1 Expression in Mouse Medial Pallium

Mikihito Shibata,¹ Daisuke Kurokawa,¹ Hiromi Nakao, Tomomi Ohmura,¹ and Shinichi Aizawa^1,2

Laboratories for ¹Vertebrate Body Plan and ²Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN Kobe, Chuo-ku, Kobe 650-0046, Japan

Correspondence should be addressed to Shinichi Aizawa, Laboratories for Vertebrate Body Plan and Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0046, Japan. Email: saizawa{at}cdb.riken.jp

Vertebrate brain hosts a diverse collection of microRNAs, but little is known about their functions in vivo. Here we propose that mouse microRNA-9 (miR-9) targets Foxg1 mRNAs for proper generation of Cajal–Retzius cells in the medial pallium. miR-9 expression is mediolaterally graded, being most intense in the cortical hem; it contrasts with the Foxg1 expression in a reciprocal gradient. The 3' untranslated regions of tetrapod, but not of teleost, Foxg1 mRNAs conserve miR-9 target sequences and are regulated by miR-9. Gain- and loss-of-function analyses of miR-9 showed that miR-9 negatively regulates endogenous Foxg1 protein level. Moreover, miR-9 overexpression in developing telencephalon at E11.5 by electroporation resulted in ectopic Reelin-positive cells over the cortex beyond the marginal zone. In addition, inhibition of endogenous miR-9 function by antisense oligonucleotides caused the regression of Wnt3a-positive cortical hem and reduction of reelin-, p73-, and NeuroD1-positive cells.

Key words: microRNA-9; Foxg1; telencephalon; medial pallium; Reelin; Cajal–Retzius cells

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Received July 10, 2008; accepted Aug. 18, 2008.

Correspondence should be addressed to Shinichi Aizawa, Laboratories for Vertebrate Body Plan and Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0046, Japan. Email: saizawa{at}cdb.riken.jp

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