Cerebral Cortex Advance Access originally published online on April 24, 2009
Cerebral Cortex 2009 19(Supplement 1):i120-i125; doi:10.1093/cercor/bhp033
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This article appears in the following Cerebral Cortex issue: Cortical Development: Neural Stem Cells to Neural Circuits Chania, Greece, May 22-25, 2008 [View the issue table of contents]
New and Improved Tools for In Utero Electroporation Studies of Developing Cerebral Cortex
Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA
Address correspondence to Joe LoTurco, PhD, Department of Physiology and Neurobiology, 75 N Eagleville Road, University of Connecticut, Storrs, CT 06269-3156, USA. Email: Joseph.LoTurco{at}uconn.edu.
In utero electroporation (IUE) has become a method of choice for rapid gain and loss of function studies in embryonic cerebral cortex. In this review we highlight some of the proven and recent advances in IUE technology that make it applicable to an increasingly wide array of experiments requiring spatial and temporal control of gene expression. Recently, cell-type–specific promoters and tamoxifen-gated cre-recombinase have been shown to work effectively with IUE. Experiments can now be designed and carried out to test whether and which cell-type–specific mechanisms operate within defined periods of neuronal migration and maturation. We have recently adapted this conditional expression approach to implement conditional rescue experiments. In conditional rescue, expression of an RNA interference (RNAi) target is restored by tamoxifen-induced cre-mediated recombination. An initial disruption in migration, and resultant malformation, caused by DCX RNAi was reversed by delayed re-expression of Dcx. In the future, combinations of spatially directed, cell-type–specific, and tamoxifen-gated transgene expression can be used to address the complex mechanisms likely to operate during development of cerebral cortex.
Key Words: migration neocortex transgenesis stem cell