Current Research Interests:
The two main areas of research in the Turner lab focus on the transcriptional control of neuronal differentiation and on small RNA-mediated control of gene expression in the mammalian nervous system.
During development of the nervous system, the formation of neurons is regulated in part by a family of transcription factors known as basic helix-loop-helix (bHLH) proteins. Several of these bHLH proteins (e.g. MASH1, neurogenin1-3) are expressed in subsets of neural progenitor cells, and can direct the initiation of neuronal differentiation, as well as other events such as cell cycle exit. We are interested in understanding the cascade of gene expression and regulatory processes initiated by the neural bHLH proteins. Ongoing studies are focused on identifying neural genes regulated by bHLH proteins, and on the link between the bHLH proteins and signaling pathways that the control cell cycle exit during neurogenesis. The discovery of small RNA-mediated gene regulation has provided novel tools for biologists. RNA interference (RNAi) is now widely used to analyze gene function. We have developed both RNA polymerase III-based and RNA polymerase II-based expression vectors for mammalian RNAi. We are using these tools to study the function of genes regulated by the neural bHLH proteins.
Over the past several years, it has become apparent that numerous endogenous small RNAs contribute to the regulation of genes in mammals. At least several hundred genes in mammals encode microRNAs (miRNAs) MiRNAs are ~22 nucleotide RNAs that regulate the translation and stability of target mRNAs via sequence-specific interactions. We have developed an in situ hybridization technique for visualizing the expression of miRNAs in mammalian tissue sections. We also are using deep sequencing technology to profile miRNAs in both wild-type and mutant mice. The long-term goal of these studies is to determine the functional roles of miRNAs in the nervous system.
Farah, M. H., Olson, J. M., Sucic, H. B., Hume, R. I., Tapscott, S. J., and Turner, D. L. (2000). Generation of neurons by transient expression of neural bHLH proteins in mammalian cells. Development: 127, 693-702.
Yu, J-Y., DeRuiter, S. L., and Turner, D. L. (2002). RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc. Natl. Acad. Sci. USA, Vol. 99: 6047-6052.
Chung, K-H. Hart, C.C., Al-Bassam, S., Avery, A., Taylor, J., Patel, P.D., Vojtek, A.B., and Turner D.L. (2006). Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155. Nucleic Acids Res. 34: e53.
Deo, M., Yu, J-Y., Chung, K-H., Tippens, M. and Turner, D.L. (2006). Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides. Developmental Dynamics, .235: 2538-48
Thompson, R.C., Deo, M., and Turner, D.L. (2007). Analysis of microRNA expression by in situ hybridization with RNA oligonucleotide probes. Methods 43: 153-161.
Yu, J-Y., Chung, K-H., , Deo, M., Thompson, R. C. and Turner, D. L. (2008). MicroRNA miR-124a regulates neurite outgrowth during neuronal differentiation. Exp. Cell Res. 314: 2618-2633.
Taylor, J., Chung, K-H., Figueroa, C., Zurawski, J., Dickson, H. M., Brace, E.J., Avery, A., Turner, D.L.,and Vojtek, A. B. (2008). The Scaffold Protein POSH Regulates Axon Outgrowth. Mol. Biol. Cell, in press.