Using Flp-Recombinase to Characterize Expansion ofWnt1-Expressing Neural Progenitors in the Mouse

AbstractHere we demonstrate how a Flp recombinase-based tagging system can be used to link temporally distinct developmental events in the mouse. By directly following Flp-mediated DNA rearrangements we have analyzed the adult expansion of embryonic neural progenitors which transiently express the signaling factor Wnt1. We reportWnt1promoter activity in embryonic cells that give rise to aspects of the adult midbrain, cerebellum, spinal cord, and dorsal root ganglia. These findings show that cells transiently expressingWnt1play more than an inductive role during early brain regionalization, giving rise to distinct adult brain regions as well as neural crest derivatives. Moreover, these results reveal two new features of the Flp–FRTsystem: First, Flp(F70L) can effectively recombine target sites (FRTs) placed in an endogenous locus in a variety of tissuesin vivo,despite previousin vitroevidence of thermolability; and second, Flp(F70L) action can be predictably and tightly regulated in the mouse embryo, making it suitable for fate mapping applications. A further advantage of the Flp–FRTsystem is that marked lineages can ultimately be combined with germline mutations and deficiencies currently being generated using the Cre–loxPrecombination system—in this way it should be possible to analyze mutant gene activities directly for their effect on cell fate