Site Specific Recombinases (SSRs): Dre & Rox-stop-Rox Reporters

An approach to independently genetically label two lineages is shown in the diagram to the right. Individual panels show independent labeling of the first heart field using a Tbx5-CreERT2/+ allele and a R26-lsl-lacZ reporter, as well as labeling of the second heart field using the Mef2c-AHF-::DreERT2 transgene transgene and a R26-rsr-lacZ reporter (images from Devine WP et al., Elife, 2014). The final panel below, and the mating diagram, show a three color scheme where all unrecombined cells express myr-tdTomato and nls-Kate, but upon Cre recombination of the mTmG allele, cells express myr-EGFP, while after Dre-mediated recombination of the nKmB reporter cells express myr-BFP. The bottom panel on the right shows the that the two lineages fail to extensively overlap after tamoxifen induction of SSR activity at E6.5 (prior to cardiac crescent formation).

Other strategies exist, such as INTERSECTIONAL GENETICS, to determine the overlap between two lineages or populations of cells.