1 Tsien, R.Y. The green fluorescent protein. Annu. Rev. Biochem. 67, 509–544 (1998).

2 Heim, R. & Tsien, R.Y. Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr. Biol. 6, 178–182 (1996).

3 Rizzo, M.A., Springer, G.H., Granada, B. & Piston, D.W. An improved cyan fluorescent protein variant useful for FRET. Nat. Biotechnol. 22, 445–449 (2004).

4 Shagin, D.A. et al. GFP-like proteins as ubiquitous metazoan superfamily: evolution of functional features and structural complexity. Mol. Biol. Evol. 21, 841–850 (2004).

5 Ai, H.W., Henderson, J.N., Remington, S.J. & Campbell, R.E. Directed evolution of a monomeric, bright and photostable version of Clavularia cyan fluorescent protein: structural characterization and applications in fluorescence imaging. Biochem. J. 400, 531–540 (2006).

6 Subach, O.M. et al. Conversion of red fluorescent protein into a bright blue probe. Chem. Biol. 15, 1116–1124 (2008).

7 Ai, H.W., Shaner, N.C., Cheng, Z., Tsien, R.Y. & Campbell, R.E. Exploration of new chromophore structures leads to the identification of improved blue fluorescent proteins. Biochemistry 46, 5904–5910 (2007).

8 Karasawa, S., Araki, T., Nagai, T., Mizuno, H. & Miyawaki, A. Cyan-emitting and orange-emitting fluorescent proteins as a donor/acceptor pair for fluorescence resonance energy transfer. Biochem. J. 381, 307–312 (2004).

9 Shaner, N.C. et al. Improving the photostability of bright monomeric orange and red fluorescent proteins. Nat. Methods 5, 545–551 (2008).

10 Shaner, N.C. et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat. Biotechnol. 22, 1567–1572 (2004).

11 Shcherbo, D. et al. Far-red fluorescent tags for protein imaging in living tissues. Biochem. J. 418, 567–574 (2009).

12 Shcherbo, D. et al. Near-infrared fluorescent proteins. Nat. Methods 7, 827–829 (2010).

13 Shaner, N.C., Steinbach, P.A. & Tsien, R.Y. A guide to choosing fluorescent proteins. Nat. Methods 2, 905–909 (2005).

14 Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

15 Livet, J. et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56–62 (2007).

16 Branda, C.S. & Dymecki, S.M. Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice. Dev. Cell 6, 7–28 (2004).

17 Snippert, H.J. et al. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143, 134–144 (2010).

18 Red-Horse, K., Ueno, H., Weissman, I.L. & Krasnow, M.A. Coronary arteries form by developmental reprogramming of venous cells. Nature 464, 549–553 (2010).

19 Rinkevich, Y., Lindau, P., Ueno, H., Longaker, M.T. & Weissman, I.L. Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature 476, 409–413 (2011).

20 Schepers, A.G. et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337, 730–735 (2012).

21 Tabansky, I. et al. Developmental bias in cleavage-stage mouse blastomeres. Curr. Biol. 23, 21–31 (2013).

22 Gupta, V. & Poss, K.D. Clonally dominant cardiomyocytes direct heart morphogenesis. Nature 484, 479–484 (2012).

23 Pan, Y.A., Livet, J., Sanes, J.R., Lichtman, J.W. & Schier, A.F. Multicolor Brainbow imaging in zebrafish. Cold Spring Harb. Protoc. 2011, pdb.prot5546 (2011).

24 Hampel, S. et al. Drosophila Brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns. Nat. Methods 8, 253–259 (2011).

25 Hadjieconomou, D. et al. Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster. Nat. Methods 8, 260–266 (2011).

26 Lang, C., Guo, X., Kerschensteiner, M. & Bareyre, F.M. Single collateral reconstructions reveal distinct phases of corticospinal remodeling after spinal cord injury. PLoS ONE 7, e30461 (2012).

27 Badaloni, A. et al. Transgenic mice expressing a dual, CRE-inducible reporter for the analysis of axon guidance and synaptogenesis. Genesis 45, 405–412 (2007).

28 Lichtman, J.W., Livet, J. & Sanes, J.R. A technicolour approach to the connectome. Nat. Rev. Neurosci. 9, 417–422 (2008).

29 Lakso, M. et al. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc. Natl. Acad. Sci. USA 89, 6232–6236 (1992).

30 Paterna, J.C., Moccetti, T., Mura, A., Feldon, J. & Büeler, H. Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain. Gene Ther. 7, 1304–1311 (2000).

31 Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010).

32 Hippenmeyer, S. et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 3, e159 (2005).

33 Srinivas, S. et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol. 1, 4 (2001).

34 Guo, C., Yang, W. & Lobe, C.G. A Cre recombinase transgene with mosaic, widespread tamoxifen-inducible action. Genesis 32, 8–18 (2002).

35 Zhang, X.M. et al. Highly restricted expression of Cre recombinase in cerebellar Purkinje cells. Genesis 40, 45–51 (2004).

36 Rossi, J. et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 13, 195–204 (2011).

37 Campsall, K.D., Mazerolle, C.J., De Repentingy, Y., Kothary, R. & Wallace, V.A. Characterization of transgene expression and Cre recombinase activity in a panel of Thy-1 promoter-Cre transgenic mice. Dev. Dyn. 224, 135–143 (2002).

38 Bunting, M., Bernstein, K.E., Greer, J.M., Capecchi, M.R. & Thomas, K.R. Targeting genes for self-excision in the germ line. Genes Dev. 13, 1524–1528 (1999).

39 McLeod, M., Craft, S. & Broach, J.R. Identification of the crossover site during FLP-mediated recombination in the Saccharomyces cerevisiae plasmid 2 μm circle. Mol. Cell Biol. 6, 3357–3367 (1986).

40 Schlake, T. & Bode, J. Use of mutated FLP recognition target (FRT) sites for the exchange of expression cassettes at defined chromosomal loci. Biochemistry 33, 12746–12751 (1994).

41 Peroutka, R.J., Elshourbagy, N., Piech, T. & Butt, T.R. Enhanced protein expression in mammalian cells using engineered SUMO fusions: secreted phospholipase A2. Protein Sci. 17, 1586–1595 (2008).

42 Farley, F.W., Soriano, P., Steffen, L.S. & Dymecki, S.M. Widespread recombinase expression using FLPeR (flipper) mice. Genesis 28, 106–110 (2000).

43 Awatramani, R., Soriano, P., Rodriguez, C., Mai, J.J. & Dymecki, S.M. Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat. Genet. 35, 70–75 (2003).

44 Araki, K., Okada, Y., Araki, M. & Yamamura, K. Comparative analysis of right element mutant loxP sites on recombination efficiency in embryonic stem cells. BMC Biotechnol. 10, 29 (2010).

45 Entenberg, D. et al. Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging. Nat. Protoc. 6, 1500–1520 (2011).

46 Mahou, P. et al. Multicolor two-photon tissue imaging by wavelength mixing. Nat. Methods 9, 815–818 (2012).

47 Wang, K. et al. Three-color femtosecond source for simultaneous excitation of three fluorescent proteins in two-photon fluorescence microscopy. Biomed. Opt. Express 3, 1972–1977 (2012).

48 Conchello, J.A. & Lichtman, J.W. Optical sectioning microscopy. Nat. Methods 2, 920–931 (2005).

49 Ducros, M. et al. Efficient large core fiber-based detection for multi-channel two-photon fluorescence microscopy and spectral unmixing. J. Neurosci. Methods 198, 172–180 (2011).

50 Card, J.P. et al. A dual infection pseudorabies virus conditional reporter approach to identify projections to collateralized neurons in complex neural circuits. PLoS ONE 6, e21141 (2011).