The Mechanism and Significance of Evf ncRNA regulation of the Dix genes

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There are two main goals of this project. In the first, we hope to gain a better understanding of a novel mechansim of RNA depednent transcriptional regulation. In the second, we hope to gain a better understanding of how GABAergic neuronal differentiation and migration are comtrolled. The first goal focuses on how the novel non-coding RNAs, embryonic ventral forebrain (Evf), influence transcription of the Dlx 5/6 enhancer. Evf ncRNAs are the first developmentally regulated ncRNAs to be discovered that affect the transcriptional activity of a homeodomain protein. Evf ncRNAs are also the first ncRNAs shown to cooperate and complex with a homeobox-containing transcription factor. The proposed studies would therefore be the first to investigate the in vivo role of developmentally regulated ncRNA-dependent modulation of enhancer activity. The importance of mechanistic studies of RNA function is clear from the number of regulatory RNAs thought to be involved different diseases. These include: Prader Willi Syndrome, diGeorge Syndrome, Beckwith-Wiedeman syndrome, Spinocerebellar ataxia type 8, and campomelic dysplasia.