Using Flp-recombinase to characterize expansion of Wnt1-expressing neural progenitors in the mouse

Abstract

Here 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 report Wnt1 promoter 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 expressing Wnt1 play 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-FRT system: First, Flp(F70L) can effectively recombine target sites (FRTs) placed in an endogenous locus in a variety of tissues in vivo, despite previous in vitro evidence 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-FRT system is that marked lineages can ultimately be combined with germline mutations and deficiencies currently being generated using the Cre-1oxP recombination system - in this way it should be possible to analyze mutant gene activities directly for their effect on cell fate.