regulation of emx2 expression by antisense transcripts in murine cortico-cerebral precursors监管emx2反义转录表达的小鼠cortico-cerebral体细胞.pdfVIP

Regulation of Emx2 Expression by Antisense Transcripts in Murine Cortico-Cerebral Precursors Giulia Spigoni, Chiara Gedressi, Antonello Mallamaci* International School for Advanced Studies (SISSA/ISAS), Trieste, Italy Abstract Background: Emx2 encodes for a transcription factor expressed in the embryonic intermediate mesoderm and central nervous system (CNS). It is implicated in several aspects of cerebral cortex development, including morphogenetic field specification, arealization, precursor proliferation and lamination. Four Emx2-associated antisense transcripts have been found in the urogenital system; one of them, Emx2OS, has been also detected in the adult brain. Until now, however, nothing is known about expression and function of Emx2OS in the developing CNS. Methodology/Principal Findings: By quantitative RT-PCR and in situ hybridization, we reconstructed the Emx2OS expression profile in the embryonic CNS, paying special attention to the developing cerebral cortex. Emx2OS was observed in a number of CNS structures expressing also Emx2. Within the cortex, Emx2OS was detectable in periventricular precursors, expressing the sense transcript, and peaked in newly born post-mitotic neurons not expressing such transcript. By integrating lentiviral gene delivery, RNAi, TetON technology, morpholino-mediated gene knock-down, drug-induced perturbation of gene expression, and quantitative RT-PCR, we addressed possible roles of Ex2 antisense RNA in Emx2 regulation, in primary CNS precursor cultures. We found that, in both cortical precursors and their neuronal progenies, Emx2 antisense RNA contributes to post-transcriptional down-regulation of its sense partner, possibly by a Dice