Tang, Jonathan C YRudolph, StephanieDhande, Onkar SAbraira, Victoria EChoi, SeungwonLapan, SylvainDrew, Iain RDrokhlyansky, EugeneHuberman, Andrew DRegehr, WadeCepko, Constance2016-05-022016Tang, J. C. Y., S. Rudolph, O. S. Dhande, V. E. Abraira, S. Choi, S. Lapan, I. R. Drew, et al. 2016. “Cell Type-Specific Manipulation with GFP-Dependent Cre Recombinase.” Nature neuroscience 18 (9): 1334-1341. doi:10.1038/nn.4081. http://dx.doi.org/10.1038/nn.4081.1097-6256http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860125Summary There are many transgenic GFP reporter lines that allow visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. Here we report the creation of a method that exploits GFP for gene manipulation, Cre Recombinase Dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, leading to effective recombination selectively in GFP-labeled cells. Further, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP+ cells, we demonstrate that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins.en-USJournal Article2016-05-0210.1038/nn.4081